Spatiotemporal pattern recognition for neurological event detection and prediction in an implantable device

ABSTRACT

A system and method for detecting and predicting neurological events with an implantable device uses a relatively low-power central processing unit in connection with signal processing circuitry to identify features (including half waves) and calculate window-based characteristics (including line lengths and areas under the curve of the waveform) in one or more electrographic signals received from a patient&#39;s brain. The features and window-based characteristics are employed within the framework of a programmable finite state machine to identify patterns and sequences in and across the electrographic signals, facilitating early and reliable detection and prediction of complex spatiotemporal neurological events in real time, and enabling responsive action by the implantable device.

CROSS REFERENCE TO RELATED APPLICATION

This is a divisional of U.S. patent application Ser. No. 10/244,093,filed Sep. 13, 2002.

FIELD OF THE INVENTION

The invention relates to systems and methods for detecting andpredicting neurological dysfunction characterized by abnormalelectrographic patterns, and more particularly to a system and methodfor detecting and predicting epileptic seizures and their onsets byanalyzing temporal and spatiotemporal patterns and sequences ofelectroencephalogram and electrocorticogram signals with an implantabledevice.

BACKGROUND OF THE INVENTION

Epilepsy, a neurological disorder characterized by the occurrence ofseizures (specifically episodic impairment or loss of consciousness,abnormal motor phenomena, psychic or sensory disturbances, or theperturbation of the autonomic nervous system), is debilitating to agreat number of people. It is believed that as many as two to fourmillion Americans may suffer from various forms of epilepsy. Researchhas found that its prevalence may be even greater worldwide,particularly in less economically developed nations, suggesting that theworldwide figure for epilepsy sufferers may be in excess of one hundredmillion.

Because epilepsy is characterized by seizures, its sufferers arefrequently limited in the kinds of activities they may participate in.Epilepsy can prevent people from driving, working, or otherwiseparticipating in much of what society has to offer. Some epilepsysufferers have serious seizures so frequently that they are effectivelyincapacitated.

Furthermore, epilepsy is often progressive and can be associated withdegenerative disorders and conditions. Over time, epileptic seizuresoften become more frequent and more serious, and in particularly severecases, are likely to lead to deterioration of other brain functions(including cognitive function) as well as physical impairments.

The current state of the art in treating neurological disorders,particularly epilepsy, typically involves drug therapy and surgery. Thefirst approach is usually drug therapy.

A number of drugs are approved and available for treating epilepsy, suchas sodium valproate, phenobarbital/primidone, ethosuximide, gabapentin,phenytoin, and carbamazepine, as well as a number of others.Unfortunately, those drugs typically have serious side effects,especially toxicity, and it is extremely important in most cases tomaintain a precise therapeutic serum level to avoid breakthroughseizures (if the dosage is too low) or toxic effects (if the dosage istoo high). The need for patient discipline is high, especially when apatient's drug regimen causes unpleasant side effects the patient maywish to avoid.

Moreover, while many patients respond well to drug therapy alone, asignificant number (at least 20-30%) do not. For those patients, surgeryis presently the best-established and most viable alternative course oftreatment.

Currently practiced surgical approaches include radical surgicalresection such as hemispherectomy, corticectomy, lobectomy and partiallobectomy, and less-radical lesionectomy, transection, and stereotacticablation. Besides being less than fully successful, these surgicalapproaches generally have a high risk of complications, and can oftenresult in damage to eloquent (i.e., functionally important) brainregions and the consequent long-term impairment of various cognitive andother neurological functions. Furthermore, for a variety of reasons,such surgical treatments are contraindicated in a substantial number ofpatients. And unfortunately, even after radical brain surgery, manyepilepsy patients are still not seizure-free.

Electrical stimulation is an emerging therapy for treating epilepsy.However, currently approved and available electrical stimulation devicesapply continuous electrical stimulation to neural tissue surrounding ornear implanted electrodes, and do not perform any detection—they are notresponsive to relevant neurological conditions.

The NeuroCybernetic Prosthesis (NCP) from Cyberonics, for example,applies continuous electrical stimulation to the patient's vagus nerve.This approach has been found to reduce seizures by about 50% in about50% of patients. Unfortunately, a much greater reduction in theincidence of seizures is needed to provide substantial clinical benefit.

The Activa device from Medtronic is a pectorally implanted continuousdeep brain stimulator intended primarily to treat Parkinson's disease.In operation, it supplies a continuous electrical pulse stream to aselected deep brain structure where an electrode has been implanted.Continuous stimulation of deep brain structures for the treatment ofepilepsy has not met with consistent success. To be effective interminating seizures, it is believed that one effective site wherestimulation should be performed is near the focus of the epileptogenicregion. The focus is often in the neocortex, where continuousstimulation may cause significant neurological deficit with clinicalsymptoms including loss of speech, sensory disorders, or involuntarymotion. Accordingly, research has been directed toward automaticresponsive epilepsy treatment based on a detection of imminent seizure.

A typical epilepsy patient experiences episodic attacks or seizures,which are generally electrographically defined as periods of abnormalneurological activity. As is traditional in the art, such periods shallbe referred to herein as “ictal”.

Most prior work on the detection and responsive treatment of seizuresvia electrical stimulation has focused on analysis ofelectroencephalogram (EEG) and electrocorticogram (ECoG) waveforms. Incommon usage, the term “EEG” is often used to refer to signalsrepresenting aggregate neuronal activity potentials detectable viaelectrodes applied to a patient's scalp, though the term can also referto signals obtained from deep in the patient's brain via depthelectrodes and the like. Specifically, “ECoGs” refer to signals obtainedfrom internal electrodes near the surface of the brain (generally on orunder the dura mater); an ECoG is a particular type of EEG. Unless thecontext clearly and expressly indicates otherwise, the term “EEG” shallbe used generically herein to refer to both EEG and ECoG signals,regardless of where in the patient's brain the electrodes are located.

Much of the work on detection has focused on the use of time-domainanalysis of EEG signals. See, e.g., J. Gotman, Automatic seizuredetection: improvements and evaluation, Electroencephalogr. Clin.Neurophysiol. 1990; 76(4): 317-24. In a typical time-domain detectionsystem, EEG signals are received by one or more implanted electrodes andthen processed by a control module, which then is capable of performingan action (intervention, warning, recording, etc.) when an abnormalneurological event is detected.

It is generally preferable to be able to detect and treat a seizure ator near its beginning, or even before it begins. The beginning of aseizure is referred to herein as an “onset.” However, it is important tonote that there are two general varieties of seizure onsets. A “clinicalonset” represents the beginning of a seizure as manifested throughobservable clinical symptoms, such as involuntary muscle movements orneurophysiological effects such as lack of responsiveness. An“electrographic onset” refers to the beginning of detectableelectrographic activity indicative of a seizure. An electrographic onsetwill frequently occur before the corresponding clinical onset, enablingintervention before the patient suffers symptoms, but that is not alwaysthe case. In addition, there are changes in the EEG that occur secondsor even minutes before the electrographic onset that can be identifiedand used to facilitate intervention before electrographic or clinicalonsets occur. This capability would be considered seizure prediction, incontrast to the detection of a seizure or its onset.

In the Gotman system, EEG waveforms are filtered and decomposed into“features” representing characteristics of interest in the waveforms.One such feature is characterized by the regular occurrence (i.e.,density) of half-waves exceeding a threshold amplitude occurring in aspecified frequency band between approximately 3 Hz and 20 Hz,especially in comparison to background (non-ictal) activity. When suchhalf-waves are detected, it is believed that seizure activity isoccurring For related approaches, see also H. Qu and J. Gotman, Aseizure warning system for long term epilepsy monitoring, Neurology1995; 45: 2250-4; and H. Qu and J. Gotman, A Patient-Specific Algorithmfor the Detection of Seizure Onset in Long-Term EEG Monitoring: PossibleUse as a Warning Device, IEEE Trans. Biomed. Eng. 1997; 44(2): 115-22.

The Gotman articles address half wave characteristics in general, andintroduce a variety of measurement criteria, including a ratio ofcurrent epoch amplitude to background; average current epoch EEGfrequency; average background EEG frequency; coefficient of variation ofwave duration; ratio of current epoch amplitude to the amplitude of thefollowing time period; average wave amplitude; average wave duration;dominant frequency (peak frequency of the dominant peak); and averagepower in a main energy zone. These criteria are variously mapped into ann-dimensional space, and whether a seizure is detected depends on thevector distance between the parameters of a measured segment of EEG anda seizure template in that space.

It should be noted that the schemes set forth in the above articles arenot tailored for use in an implantable device, and hence typicallyrequire more computational ability than would be available in such adevice.

U.S. Pat. No. 6,018,682 to Rise describes an implantable seizure warningsystem that implements a form of the Gotman system. However, the systemdescribed therein uses only a single detection modality, namely a countof sharp spike and wave patterns within a time period. This isaccomplished with relatively complex processing, including averagingover time and quantifying sharpness by way of a second derivative of thesignal. The Rise patent does not disclose how the signals are processedat a low level, nor does it explain detection criteria in any specificlevel of detail.

A more computationally demanding approach is to transform EEG signalsinto the frequency domain for rigorous spectrum analysis. See, e.g.,U.S. Pat. No. 5,995,868 to Dorfmeister et al., which analyzes the powerspectral density of EEG signals in comparison to backgroundcharacteristics. Although this approach is generally believed to achievegood results, for the most part, its computational expense renders itless than optimal for use in long-term implanted epilepsy monitor andtreatment devices. With current technology, the battery life in animplantable device computationally capable of performing the Dorfmeistermethod would be too short for it to be feasible.

Also representing an alternative and more complex approach is U.S. Pat.No. 5,857,978 to Hively et al., in which various non-linear andstatistical characteristics of EEG signals are analyzed to identify theonset of ictal activity. Once more, the calculation of statisticallyrelevant characteristics is not believed to be feasible in animplantable device.

U.S. Pat. No. 6,016,449 to Fischell, et al. (which is herebyincorporated by reference as though set forth in full herein), describesan implantable seizure detection and treatment system. In the Fischellsystem, various detection methods are possible, all of which essentiallyrely upon the analysis (either in the time domain or the frequencydomain) of processed EEG signals. Fischell's controller is preferablyimplanted intracranially, but other approaches are also possible,including the use of an external controller. The processing anddetection techniques applied in Fischell are generally well suited forimplantable use. When a seizure is detected, the Fischell system appliesresponsive electrical stimulation to terminate the seizure, a capabilitythat will be discussed in further detail below.

All of these approaches provide useful information, and in some casesmay provide sufficient information for accurate detection and predictionof most imminent epileptic seizures.

However, the known approaches generally observe electrographic patternsat a single moment in time (or over a region of time reduced to one ormore features); they do not differentiate between different patterns orsequences of electrographic activity, separated in time or space. It isbelieved that spatiotemporal patterns and sequences may serve todistinguish activity of interest from background activity, where lookingat small portions of signals in isolation might not.

Neurological events are often characterized by evolving patterns andsequences of activity. For example, seizure onsets are often defined bydifferent morphological patterns. See, e.g., Spencer S S, Guimaraes P,Katz A, Kim J, Spencer D. Morphological patterns of seizures recordedintracranially. Epilepsia 1992; 33: 537-545; and Lee S A, Spencer D D,Spencer S S. Intracranial EEG seizure-onset patterns in neocorticalepilepsy. Epilepsia 2000; 41: 297-307.

Even within an onset or seizure, the most prominent characteristic maybe changes in a signal rather than the signal itself at a snapshot intime. Schiff S J, Colella D, Jacyna G M et al. Brain chirps:spectrographic signatures of epileptic seizures. Clin. Neurophysiol.2000; 111: 953-958; and Bergey G K, Franaszczuk P J. Epileptic seizuresare characterized by changing signal complexity. Clin. Neurophysiol.2001; 112: 241-249.

Spatial patterns (e.g., where an onset occurs) may be related totemporal patterns and signal morphology, and vice versa. It is believedthat the most successful treatment strategies may be dependent uponseizure origin and type. Velasco A L, Wilson C L, Babb T L, Engel J Jr.Functional and anatomic correlates of two frequently observed temporallobe seizure-onset patterns. Neural Plast. 2000; 7: 49-63. Thus, itwould be desirable to be able to identify different patterns andmorphologies to provide the best possible therapy to the patient.

Spatial patterns, represented by activity from different parts of thebrain at the same time or at different times, may also come into play.For example, if it can be determined that seizure activity haspropagated from one location to another, it may be advantageous to applya therapy that takes that into account (rather than performing focalstimulation wherever the activity is first seen). See, e.g., Schiller Y,Cascino G D, Busacker N E, Sharbrough F W. Characterization andcomparison of local onset and remote propagated electrographic seizuresrecorded with intracranial electrodes. Epilepsia 1998; 39: 380-388. Anindication that a seizure has originated in a certain part of the brainmay lead to improved treatment possibilities.

It has also been shown that electrographic signatures start to evolvelong before a seizure begins. Litt B, Esteller R, Echauz J et al.Epileptic seizures may begin hours in advance of clinical onset: areport of five patients. Neuron 2001; 30: 51-64. Accordingly, seizureprediction may be accomplished by identifying this slow evolution ofsignal characteristics over time, leading to the possibility ofeffective preventative therapy. Present state-of-the-art seizure andneurological event detection technologies are generally based upon asingle combination of characteristics—representative of a currentneurological point in time or derived from a feature that tends to smeartogether signal characteristics over a time period.

Accordingly, and for the reasons set forth above, it would beadvantageous to have the benefit of a neurological event detector thatis capable of resolving time sequences and correlating spatial patterns.Such a detector would be capable of identifying temporal, spatial, andspatiotemporal patterns and sequences of neurological activity. Asdescribed above, this would tend to facilitate improved detectionperformance, improved therapy, and the possibility of accurate seizureprediction.

Two types of detection errors are generally possible. A “falsepositive,” as the term is used herein, refers to a detection of aseizure or ictal activity when no seizure or other abnormal event isactually occurring. Similarly, a “false negative” herein refers to thefailure to detect a seizure or ictal activity that actually is occurringor shortly will occur.

In most cases, with all known implementations of the known approaches todetecting abnormal seizure activity solely by monitoring and analyzingindividual segments of EEG activity, when a seizure detection algorithmis tuned to catch all seizures, there will be a significant number offalse positives. While it is currently believed that there are minimalor no side effects to limited amounts of over-stimulation (e.g.,providing stimulation sufficient to terminate a seizure in response to afalse positive), the possibility of accidentally initiating a seizure orincreasing the patient's susceptibility to seizures must be considered.

As is well known, it has been suggested that it is possible to treat andterminate seizures by applying electrical stimulation to the brain. See,e.g., U.S. Pat. No. 6,016,449 to Fischell et al., and H. R. Wagner, etal., Suppression of cortical epileptiform activity by generalized andlocalized ECoG desynchronization, Electroencephalogr. Clin.Neurophysiol. 1975; 39(5): 499-506. And as stated above, it is believedto be beneficial to perform this stimulation only when a seizure (orother undesired neurological event) is occurring or about to occur, asinappropriate stimulation may result in the initiation of seizures.

Furthermore, it should be noted that a false negative (that is, aseizure that occurs without any warning or treatment from the device)will often cause the patient significant discomfort and detriment.Clearly, false negatives are to be avoided.

It has been found to be difficult to achieve an acceptably low level offalse positives and false negatives with the level of computationalability available in an implantable device with reasonable battery life.

Preferably, the battery in an implantable device, particularly oneimplanted intracranially, should last at least several years. There is asubstantial risk of complications (such as infection, blood clots, andthe overgrowth of scar tissue) and lead failure each time an implanteddevice or its battery is replaced. Rechargeable batteries have not beenfound to provide any advantage in this regard, as they are not asefficient as traditional cells, and the additional electronic circuitryrequired to support the recharging operation contributes to the device'ssize and complexity. Moreover, there is a need for patient discipline inrecharging the device batteries, which calls for the frequenttransmission of a substantial amount of power over a wireless link andthrough the patient's skin and other tissue.

As stated above, the detection and prediction of ictal activity hastraditionally required a significant amount of computational ability.Moreover, for an implanted device to have significant real-worldutility, it is also advantageous to include a number of other featuresand capabilities. Specifically, treatment (via electrical stimulation ordrug infusion) and/or warning (via an audio annunciator, for example),recording of EEG signals for later consideration and analysis, andtelemetry providing a link to external equipment are all usefulcapabilities for an implanted device capable of detecting or predictingepileptiform signals. All of these additional subsystems will consumefurther power.

Moreover, size is also a consideration. For various reasons,intracranial implants are favored. A device implanted intracranially (orunder the scalp) will typically have a lower risk of failure than asimilar device implanted pectorally or elsewhere, which require a leadto be run from the device, through the patient's neck to the electrodeimplantation sites in the patient's head. This lead is also prone toreceive additional electromagnetic interference.

As is well known in the art, the computational ability of aprocessor-controlled system is directly related to both size and powerconsumption. In accordance with the above considerations, therefore, itwould be advantageous to have sufficient detection and predictioncapabilities to avoid a substantial number of false positive and falsenegative detections, and yet consume little enough power (in conjunctionwith the other subsystems) to enable long battery life. Such animplantable device would have a relatively low-power central processingunit to reduce the electrical power consumed by that portion.

At the current time, there is no known implantable device that iscapable of detecting and predicting seizures based on spatiotemporalpatterns and sequences.

SUMMARY OF THE INVENTION

Accordingly, an implantable device according to the invention fordetecting and predicting epileptic seizures includes a relativelylow-speed and low-power central processing unit, as well as customizedelectronic circuit modules in a detection subsystem. As describedherein, the detection subsystem also performs prediction, which in thecontext of the present application is a form of detection that occursbefore identifiable clinical symptoms or even obvious electrographicpatterns are evident upon inspection. The sane methods, potentially withdifferent parameters, are adapted to be used for both detection andprediction. Generally, as described herein, a neurological event (suchas an epileptic seizure) may be detected, an electrographic “onset” ofsuch a neurological event (an electrographic indication of an eventoccurring at the same time as or before the clinical event begins) maybe detected (and may be characterized by different waveform observationsthan the event itself), and a “precursor” to a neurological event(electrographic activity regularly occurring some time before theclinical event) may be detected as predictive of the neurological event.

As described herein and as the terms are generally understood, thepresent approach is generally not statistical or stochastic in nature.The invention, and particularly the detection subsystem thereof, isspecifically adapted to perform much of the signal processing andanalysis requisite for accurate and effective neurological eventdetection. The central processing unit remains in a suspended “sleep”state characterized by relative inactivity a substantial percentage ofthe time, and is periodically awakened by interrupts from the detectionsubsystem to perform certain tasks related to the detection andprediction schemes enabled by the device.

Much of the processing performed by an implantable system according tothe invention involves operations on digital data in the time domain.Preferably, to reduce the amount of data processing required by theinvention, samples at ten-bit resolution are taken at a rate less thanor equal to approximately 500 Hz (2 ms per sample).

As stated above, an implantable system according to the invention iscapable of accurate and reliable seizure detection and prediction. Toaccomplish this, the invention employs a combination of signalprocessing and analysis modalities, including data reduction and featureextraction techniques, mostly implemented as customized digitalelectronics modules, minimally reliant upon a central processing unit.

In particular, it has been found to be advantageous to utilize twodifferent data reduction methodologies, both of which collect datarepresentative of EEG signals within a sequence of uniform time windowseach having a specified duration.

The first data reduction methodology involves the calculation of a “linelength function” for an EEG signal within a time window. The second datareduction methodology involves the calculation of an “area function”represented by an EEG signal within a time window. The centralprocessing unit receives the line length function and area functionmeasurements performed by the detection subsystem, and is capable ofacting based on those measurements or their trends.

Feature extraction, specifically the identification of half waves in anEEG signal, also provides useful information. A half wave is an intervalbetween a local waveform minimum and a local waveform maximum; each timea signal “changes direction” (from increasing to decreasing, or viceversa), subject to limitations that will be set forth in further detailbelow, a new half wave is identified.

To capture and identify patterns and sequences of activity, such as theevolving signals that characterize seizure onsets and pre-onsetactivity, the invention employs a programmable finite state machinearchitecture to model the behavior of the patient's brain in the moments(seconds, minutes, or even hours) leading up to a seizure or otherneurological event of interest. The state machine employed by theinvention is capable of identifying patterns and sequences over time andspace, thereby distinguishing complex seizure or onset signal activityfrom background activity that might otherwise contain certain signalcharacteristics that are similar to those in the seizure or onset.

The approach set forth herein is similar in some ways to templatematching, but with extensive programmability and configurability.Flexibility in configurations, times, and sequences is facilitated by animplementation of a finite state machine that is well suited for use ina low power implantable device.

Accordingly, in one embodiment of the invention, a system according tothe invention includes a central processing unit, as well as a detectionsubsystem that further includes a waveform analyzer. The waveformanalyzer includes waveform feature analysis capabilities (such as halfwave characteristics) as well as window-based analysis capabilities(such as line length and area under the curve), and both aspects arecombined to provide enhanced neurological event detection. Custom finitestate machines are programmed and employed within the system to identifypatterns and sequences within the electrographic activity that makes upthe neurological event of interest. A central processing unit is used toconsolidate the results from multiple channels and coordinate responsiveaction when necessary.

The method is generally performed by analyzing electrographic signalswith the line length, area, and half wave analysis tools describedabove, and employing a time-dependent finite state machine to identify asequence or pattern of wave characteristics, either from a singlegeneral location in the patient's brain or from multiple locations overtime. The process is relatively computationally efficient, in thatdedicated hardware subsystems are employed where possible to reducepower consumption and allow the central processing unit to remain in arelatively low power state for as much time as possible.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features, and advantages of the invention willbecome apparent from the detailed description below and the accompanyingdrawings, in which:

FIG. 1 is an exemplary time-independent state transition diagramrepresenting a finite state machine and including several possiblesequences of signal events leading to a neurological event detectionaccording to the invention;

FIG. 2 is an exemplary electrographic waveform including a sequence ofseveral signal types adapted for detection with a system according tothe invention;

FIG. 3 is a schematic illustration of a patient's head showing theplacement of an implantable neurostimulator according to an embodimentof the invention;

FIG. 4 is a schematic illustration of a patient's cranium showing theimplantable neurostimulator of FIG. 3 as implanted, including leadsextending to the patient's brain;

FIG. 5 is a block diagram illustrating the major functional subsystemsof an implantable neurostimulator according to the invention;

FIG. 6 is a block diagram illustrating a system context in which animplantable neurostimulator according to the invention is implanted andoperated;

FIG. 7 is a block diagram illustrating the functional components of thedetection subsystem of the implantable neurostimulator shown in FIG. 6;

FIG. 8 is a block diagram illustrating the functional components of thesensing front end of the detection subsystem of FIG. 7;

FIG. 9 is a block diagram illustrating the components of the waveformanalyzer of the detection subsystem of FIG. 7;

FIG. 10 is a block diagram illustrating the functional arrangement ofcomponents of the waveform analyzer of the detection subsystem of FIG. 7in one possible programmed embodiment of the invention;

FIG. 11 is a graph of an exemplary EEG signal, illustratingdecomposition of the signal into time windows and samples;

FIG. 12 is a graph of the exemplary EEG signal of FIG. 11, illustratingthe extraction of half waves from the signal;

FIG. 13 is a flow chart illustrating the process performed by hardwarefunctional components of the waveform analyzer of FIG. 9 in extractinghalf waves as illustrated in FIG. 12;

FIG. 14 is a flow chart illustrating the process performed by softwarein the central processing unit in extracting and analyzing half wavesfrom an EEG signal;

FIG. 15 is a flow chart illustrating the process performed by softwarein the central processing unit in the application of an X of Y criterionto half wave windows;

FIG. 16 is a graph of the exemplary EEG signal of FIG. 11, illustratingthe calculation of a line length function;

FIG. 17 is a flow chart illustrating the process performed by hardwarefunctional components of the waveform analyzer of FIG. 9 in calculatingthe line length function as illustrated in FIG. 16;

FIG. 18 is a flow chart illustrating the process performed by softwarein the central processing unit in calculating and analyzing the linelength function of an EEG signal;

FIG. 19 is a graph of the exemplary EEG signal of FIG. 11, illustratingthe calculation of an area function;

FIG. 20 is a flow chart illustrating the process performed by hardwarefunctional components of the waveform analyzer of FIG. 7 in calculatingthe area function as illustrated in FIG. 19;

FIG. 21 is a flow chart illustrating the process performed by softwarein the central processing unit in calculating and analyzing the areafunction of an EEG signal;

FIG. 22 is an unconfigured state transition diagram as embodied in anunprogrammed implantable device according to the invention;

FIG. 23 is the state transition diagram of FIG. 1 as represented in aprogrammed implantable device according to the invention;

FIG. 24 is an exemplary time-dependent state transition diagramrepresenting a finite state machine and including several possiblesequences of signal events leading to a neurological event detectionaccording to the invention;

FIG. 25 is the state transition diagram of FIG. 24 as represented in aprogrammed implantable device according to the invention;

FIG. 26 is a flow chart illustrating the sequence of steps performed bya system according to the invention in detecting and predicting patternsvia the state machine implementation of the invention upon theidentification of a signal event;

FIG. 27 is a flow chart illustrating the process performed byevent-driven software in the central processing unit to analyze halfwave, line length, and area information for detection according to theinvention;

FIG. 28 is a flow chart illustrating the combination of analysis toolsinto detection channels in an embodiment of the invention;

FIG. 29 is a flow chart illustrating the combination of detectionchannels into event detectors in an embodiment of the invention;

FIG. 30 is a flow chart illustrating the steps performed in evaluating astate machine instance according to the procedure of FIG. 26;

FIG. 31 is a flow chart illustrating the steps performed in time-basedprocessing of state machine instances according to the invention;

FIG. 32 is a flow chart illustrating the steps performed in processingtransitions from an initial state according to the procedure of FIG. 26;

FIG. 33 is a flow chart illustrating the steps performed in updating astate machine instance to perform a transition according to theprocedure of FIG. 30; and

FIG. 34 is a flow chart illustrating the steps performed intransitioning from one state to another as illustrated in FIG. 33 in asystem according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention is described below, with reference to detailedillustrative embodiments. It will be apparent that a system according tothe invention may be embodied in a wide variety of forms. Consequently,the specific structural and functional details disclosed herein arerepresentative and do not limit the scope of the invention.

As described above, a system according to the invention is capable ofidentifying patterns and sequences, both in time and across variouslocations in the brain, for the purpose of detecting and in some casespredicting neurological events of interest. In the disclosed embodimentof the invention, specially adapted and implemented finite statemachines are employed to achieve this objective. These state machinesare described in detail below.

A finite state machine is a mathematical model capable of representingthe behavior of a system based on its current state and inputs thesystem is exposed to. Typically, and as employed herein, a state machineincludes an initial state and multiple additional states to whichtransitions can be made. Inputs, in the present example system events(such as individual signal events detected by a system according to theinvention) cause the state machine to selectively transition from stateto state until a desired state is reached—either an “end” stateindicating that a desired sequence was not observed, or a “detection”state indicating that a desired sequence was observed. Accordingly, astate machine according to the invention serves as a sort of grammar forencoding patterns and sequences of events of interest, namely,physiological (or neurological) events from one or more locations in thepatient's brain or elsewhere, as well as system conditions. Thisframework allows for the identification of such patterns and sequencesthat traditional feature-extracting and window-processing detectionschemes are often unable to discriminate from baseline data.

For purposes of this disclosure, a “neurological event” is generally aclinically significant occurrence marked by at least one detectablechange in a physiological variable, such as a sequence or pattern of oneor more separately detectable “signal events” identified by a systemaccording to the invention. It should be noted that a neurological eventmay be associated with a single signal event, or may be made up of apattern or sequence of signal events identified in one or morelocations, either concurrently or at different times. A “system event”as the term is used herein refers to either a detected signal event orsome other event of interest either identified or generated by a systemaccording to the invention, such as a timer expiration or otherinterrupt; it may be clinical or non-clinical in nature.

In general, a finite state machine is represented as and its behavior isdescribed by a directed graph called a state transition diagram (orsimply a state diagram) wherein a node or vertex of the graph (shown asa circle in FIG. 1) corresponds to a state of the finite state machineand wherein a path between two nodes (shown as an arrow between twocircles in FIG. 1) corresponds to a transition from one state toanother. The directed graph representation of a finite state machineprovides an easy way to visualize the operation of the finite statemachine and, thereby, the behavior of the corresponding system.

Referring initially to FIG. 1, a state transition diagram representingan exemplary time-independent state machine 110 is set forth; such astate machine is capable of being represented by a system according tothe invention, and may represent several sequences of conditions thatmay be of interest for detecting neurological events.

In particular, hypothetically, if a neurological event of interest isdefined by a sequence of signal events, namely a “signal A” followed bya “signal B” followed by a “signal C,” or alternatively by signal Afollowed by a “signal D” followed by a “signal E,” but never includessignal A directly followed by a “signal F,” then the state machine ofFIG. 1 represents the conditions leading up to the neurological event.

In particular, starting with an initial state 112, if signal A 114 isencountered, the state machine moves to a first state 116. All of thecombinations described above begin with signal A 114. If signal A 114 isfollowed by signal B 118, then a second state 120 is achieved, and ifsignal C 122 is then observed, then a detection state 124 is reached,and a system according to the invention reacts accordingly. After thesystem acts as desired, the state machine 110 generally will be reset tothe initial state 112 for further use.

After the first state 116 is reached, if signal D 126 is observedinstead of signal B 118, then the state machine transitions to a thirdstate 128. Following that, observation of signal E 130 will cause thedetection state 124 to be reached, as above. Accordingly, two possiblesequences of signal events lead to the detection state 124: signal A114, then signal B 118, then signal C 122 (“A>B>C”); or alternatively,signal A 114, then signal D 126, then signal E 130 (“A>D>E”).

On the other hand, if after the first state 116 is reached, signal F 132is encountered, then the state machine transitions to an end state 134,and a system according to the invention performs any desired action(which may include resetting the state machine 110 to the initial state112, either immediately or after a delay or some other action).

FIG. 2 sets forth an exemplary electrographic waveform 210; it isillustrative of how sequence detection according to the invention isadvantageous.

The exemplary electrographic waveform 210 includes several differenttypes of activity: initially, background activity 212 generallyrepresenting normal brain activity; an initial higher-energy burst 214including spike-and-wave activity; a lower-amplitude high-frequencyportion 216 followed immediately by a lower-frequency rhythmic segment218; all of which is then followed by stereotypical high-amplitudehigher-frequency seizure activity 220.

It will be observed that the background activity 212, when magnified(primarily along the x-axis), is a relatively low-amplitude signal 222with little or no observable organization. Accordingly, detection toolsdescribed in detail below (and in U.S. patent application Ser. No.09/896,092, filed on Jun. 28, 2001, incorporated by reference below) aregenerally able to distinguish background activity 212 from the othertypes of activity described below and also illustrated in FIG. 2, aswell as other types of signals.

The initial higher-energy burst 214 that follows the background activity212 appears, when magnified, to include prominent spike-and-waveactivity 224 that is detectable by a system according to the inventionas set forth in detail below. Similarly, the following lower-amplitudehigh-frequency portion 216 (which when magnified shows distinctivehigh-frequency activity 226) also has detectable characteristics, asdoes the lower-frequency rhythmic segment 218 (which, when magnified,clearly shows primarily low-frequency content 228).

After the seizure activity 220 begins, a magnified portion of thewaveform illustrates higher-frequency high-amplitude activity 230; atthis point, clinical symptoms are likely to be imminent.

Preferably, a system according to the invention is able to identify theseizure activity 220 at an early point in time 232, immediately afterthe background activity 212 gives way to something else (in this case, ahigher-energy spike-and-wave burst 214). If the spike-and-wave burst 214is always followed closely by seizure activity 220 (regardless of whatcomes between), then the early point in time 232 can be considered anunequivocal electrographic onset (UEO), and it would be sufficient todetect only the distinction between the background activity and thespike-and-wave burst 214.

However, if signals similar to the spike-and-wave burst 214 occur atother times as well, and are not followed closely by seizure activity220, then the spike-and-wave burst 214 may not be an adequate indicatorof imminent seizure. It may, in this circumstance, be necessary todetect part or all of the sequence of signals 212-220 illustrated inFIG. 2, and detection may be accomplished at a later point in time 234,preferably still before clinical symptoms begin.

Accordingly, the sequence of signals illustrated in FIG. 2 is relativelycomplex, and it is expected that in actual real-world implementations ofa system according to the invention, neurological event detection andprediction can be accomplished with fewer states and less complexity.However, as will be appreciated in light of the detailed descriptionbelow, the invention described herein is sufficiently flexible toaccommodate even more complex situations.

There is no relationship between the illustrative state machinetransition diagram of FIG. 1 and the waveforms of FIG. 2, that is, thestate machine set forth in FIG. 1 does not necessarily represent anyaspect of FIG. 2. However, an analogy can be made to the terminology ofthe exemplary state machine of FIG. 1. In particular, four different“signal events” (i.e., different identified signal types) illustrated inFIG. 2 would trigger transitions between states after the initial state.While only background activity 212 is present, the state machine wouldremain in its initial state. Upon detection of the spike-and-wave burst214 (“signal A”), the state machine would transition to a first state.Upon detection of the lower-amplitude high-frequency portion 216(“signal B”), the state machine would transition to a second state. Withobservation of the lower-frequency rhythmic segment 218 (“signal C”),the state machine would transition to a third state. Seizure activity220 (“signal D”) would then prompt transition to a detection state, atwhich point therapy would be applied (or other desired action taken). Itis important to note that, as described above, the entire sequence ofsignals must occur, or a detection will not be triggered. Ifhigh-amplitude activity similar to the seizure activity 220 isoccasionally present without a seizure occurring, the sequenceidentification facilitated by the invention will tend to reduce falsepositive detections, and hence undesired therapy applications, as willbe described in further detail below.

FIG. 3 depicts an intracranially implanted device 310 according to theinvention, which in one embodiment is a small self-contained responsiveneurostimulator. As the term is used herein, a responsiveneurostimulator is a device capable of detecting or predicting ictalactivity (or other neurological events) and providing electricalstimulation to neural tissue in response to that activity, where theelectrical stimulation is specifically intended to terminate the ictalactivity, treat a neurological event, prevent an unwanted neurologicalevent from occurring, or lessen the severity or frequency of certainsymptoms of a neurological disorder. As disclosed herein, the responsiveneurostimulator detects ictal activity by systems and methods accordingto the invention.

Preferably, an implantable device according to the invention is capableof detecting or predicting any kind of neurological event that has arepresentative electrographic signature. While the disclosed embodimentis described primarily as responsive to epileptic seizures, it should berecognized that it is also possible to respond to other types ofneurological disorders, such as movement disorders (e.g. the tremorscharacterizing Parkinson's disease), migraine headaches, chronic pain,and neuropsychiatric disorders such as depression. Preferably,neurological events representing any or all of these afflictions can bedetected when they are actually occurring, in an onset stage, or as apredictive precursor before clinical symptoms begin.

In the disclosed embodiment, the neurostimulator is implantedintracranially in a patient's parietal bone 410, in a location anteriorto the lambdoidal suture 412 (see FIG. 4). It should be noted, however,that the placement described and illustrated herein is merely exemplary,and other locations and configurations are also possible, in the craniumor elsewhere, depending on the size and shape of the device andindividual patient needs, among other factors. The device 310 ispreferably configured to fit the contours of the patient's cranium 414.In an alternative embodiment, the device 310 is implanted under thepatient's scalp 312 but external to the cranium; it is expected,however, that this configuration would generally cause an undesirableprotrusion in the patient's scalp where the device is located. In yetanother alternative embodiment, when it is not possible to implant thedevice intracranially, it may be implanted pectorally (not shown), withleads extending through the patient's neck and between the patient'scranium and scalp, as necessary.

It should be recognized that the embodiment of the device 310 describedand illustrated herein is preferably a responsive neurostimulator fordetecting and treating epilepsy by detecting seizures or their onsets orprecursors, and preventing and/or terminating such epileptic seizures.

In an alternative embodiment of the invention, the device 310 is not aresponsive neurostimulator, but is an apparatus capable of detectingneurological conditions and events and performing actions in responsethereto. The actions performed by such an embodiment of the device 310need not be therapeutic, but may involve data recording or transmission,providing warnings to the patient, or any of a number of knownalternative actions. Such a device will typically act as a diagnosticdevice when interfaced with external equipment, as will be discussed infurther detail below.

The device 310, as implanted intracranially, is illustrated in greaterdetail in FIG. 4. The device 310 is affixed in the patient's cranium 414by way of a ferrule 416. The ferrule 416 is a structural member adaptedto fit into a cranial opening, attach to the cranium 414, and retain thedevice 310.

To implant the device 310, a craniotomy is performed in the parietalbone 410 anterior to the lambdoidal suture 412 to define an opening 418slightly larger than the device 310. The ferrule 416 is inserted intothe opening 418 and affixed to the cranium 414, ensuring a tight andsecure fit. The device 310 is then inserted into and affixed to theferrule 416.

As shown in FIG. 4, the device 310 includes a lead connector 420 adaptedto receive one or more electrical leads, such as a first lead 422. Thelead connector 420 acts to physically secure the lead 422 to the device310, and facilitates electrical connection between a conductor in thelead 422 coupling an electrode to circuitry within the device 310. Thelead connector 420 accomplishes this in a substantially fluid-tightenvironment with biocompatible materials.

The lead 422, as illustrated, and other leads for use in a system ormethod according to the invention, is a flexible elongated member havingone or more conductors. As shown, the lead 422 is coupled to the device310 via the lead connector 420, and is generally situated on the outersurface of the cranium 414 (and under the patient's scalp 312),extending between the device 310 and a burr hole 424 or other cranialopening, where the lead 422 enters the cranium 414 and is coupled to adepth electrode (e.g., one of the electrodes 512-518 of FIG. 5)implanted in a desired location in the patient's brain. If the length ofthe lead 422 is substantially greater than the distance between thedevice 310 and the burr hole 424, any excess may be urged into a coilconfiguration under the scalp 312. As described in U.S. Pat. No.6,006,124 to Fischell, et al., which is hereby incorporated by referenceas though set forth in full herein, the burr hole 424 is sealed afterimplantation to prevent further movement of the lead 422; in anembodiment of the invention, a burr hole cover apparatus is affixed tothe cranium 414 at least partially within the burr hole 424 to providethis functionality.

The device 310 includes a durable outer housing 426 fabricated from abiocompatible material. Titanium, which is light, extremely strong, andbiocompatible, is used in analogous devices, such as cardiac pacemakers,and would serve advantageously in this context. As the device 310 isself-contained, the housing 426 encloses a battery and any electroniccircuitry necessary or desirable to provide the functionality describedherein, as well as any other features. As will be described in furtherdetail below, a telemetry coil may be provided outside of the housing426 (and potentially integrated with the lead connector 420) tofacilitate communication between the device 310 and external devices.

The neurostimulator configuration described herein and illustrated inFIG. 4 provides several advantages over alternative designs. First, theself-contained nature of the neurostimulator substantially decreases theneed for access to the device 310, allowing the patient to participatein normal life activities. Its small size and intracranial placementcauses a minimum of cosmetic disfigurement. The device 310 will fit inan opening in the patient's cranium, under the patient's scalp, withlittle noticeable protrusion or bulge. The ferrule 416 used forimplantation allows the craniotomy to be performed and fit verifiedwithout the possibility of breaking the device 310, and also providesprotection against the device 310 being pushed into the brain underexternal pressure or impact. A further advantage is that the ferrule 416receives any cranial bone growth, so at explant, the device 310 can bereplaced without removing any bone screws—only the fasteners retainingthe device 310 in the ferrule 416 need be manipulated.

FIG. 5 depicts a schematic block diagram of a neurostimulator systemaccording to the invention, including the implantable neurostimulatordevice 310, which in one embodiment (as described above) is a smallself-contained responsive neurostimulator that is intracraniallyimplanted. As the term is used herein, a responsive neurostimulator is adevice capable of detecting undesired activity (or other neurologicalevents) and providing electrical stimulation to neural tissue inresponse to that activity, where the electrical stimulation isspecifically intended to terminate the undesired activity, treat aneurological event, prevent an unwanted neurological event fromoccurring, or lessen the severity or frequency of certain symptoms of aneurological disorder.

It should be recognized that the embodiment of the device described andillustrated herein is preferably a responsive neurostimulator fordetecting and treating epilepsy by detecting seizure precursors andpreventing and/or terminating epileptic seizures.

FIG. 5 is an overall block diagram of the implantable neurostimulatordevice 310 used for measurement, detection, and treatment according tothe invention. Inside the housing of the neurostimulator device 310 areseveral subsystems making up the device. The implantable neurostimulatordevice 310 is capable of being coupled to a plurality of electrodes 512,514, 516, and 518 (each of which may be individually or togetherconnected to the implantable neurostimulator device 310 via one or moreleads) for sensing and stimulation. In the illustrated embodiment, thecoupling is accomplished through a lead connector. Although fourelectrodes are shown in FIG. 5, it should be recognized that any numberis possible, and in the embodiment described in detail below, eightelectrodes are used. In fact, it is possible to employ an embodiment ofthe invention that uses a single lead with at least two electrodes, ortwo leads each with a single electrode (or with a second electrodeprovided by a conductive exterior portion of the housing in oneembodiment), although bipolar sensing between two closely spacedelectrodes on a lead is preferred to minimize common mode signalsincluding noise.

The electrodes 512-518 are in contact with the patient's brain or areotherwise advantageously located to receive EEG signals or provideelectrical stimulation. Each of the electrodes 512-518 is alsoelectrically coupled to an electrode interface 520. Preferably, theelectrode interface is capable of selecting each electrode as requiredfor sensing and stimulation; accordingly the electrode interface iscoupled to a detection subsystem 522 and a stimulation subsystem 524(which, in an embodiment of the invention, may provide therapy otherthan electrical stimulation). The electrode interface may also provideany other features, capabilities, or aspects, including but not limitedto amplification, isolation, and charge-balancing functions, that arerequired for a proper interface with neurological tissue and notprovided by any other subsystem of the device 310.

The detection subsystem 522 includes and serves primarily as an EEGwaveform analyzer; detection is accomplished in conjunction with acentral processing unit (CPU) 528. The EEG waveform analyzer function isadapted to receive EEG signals from the electrodes 512-518, through theelectrode interface 520, and to process those EEG signals to identifyneurological activity indicative of a seizure or a precursor to aseizure. One way to implement such EEG analysis functionality isdisclosed in detail in U.S. Pat. No. 6,016,449 to Fischell et al.,incorporated by reference above. Additional inventive methods aredescribed in U.S. patent application Ser. No. 09/896,092 to Pless etal., filed on Jun. 28, 2001 and entitled “SEIZURE SENSING AND DETECTIONUSING AN IMPLANTABLE DEVICE,” of which details will be set forth below(and which is also hereby incorporated by reference as though set forthin full). The detection subsystem may optionally also contain furthersensing and detection capabilities, including but not limited toparameters derived from other physiological conditions (such aselectrophysiological parameters, temperature, blood pressure, etc.). Ingeneral, prior to analysis, the detection subsystem performsamplification, analog to digital conversion, and multiplexing functionson the signals in the sensing channels received from the electrodes512-518.

The stimulation subsystem 524 is capable of applying electricalstimulation to neurological tissue through the electrodes 512-518. Thiscan be accomplished in any of a number of different manners. Forexample, it may be advantageous in some circumstances to providestimulation in the form of a substantially continuous stream of pulses,or on a scheduled basis. Preferably, therapeutic stimulation is providedin response to abnormal neurological events detected by the EEG analyzerfunction of the detection subsystem 522. As illustrated in FIG. 5, thestimulation subsystem 524 and the EEG analyzer function of the detectionsubsystem 522 are in communication; this facilitates the ability ofstimulation subsystem 524 to provide responsive stimulation as well asan ability of the detection subsystem 522 to blank the amplifiers whilestimulation is being performed to minimize stimulation artifacts. It iscontemplated that the parameters of the stimulation signal (e.g.,frequency, duration, waveform) provided by the stimulation subsystem 524would be specified by other subsystems in the implantable device 310, aswill be described in further detail below.

In accordance with the invention, the stimulation subsystem 524 may alsoprovide for other types of stimulation, besides electrical stimulationdescribed above. In particular, in certain circumstances, it may beadvantageous to provide audio, visual, or tactile signals to thepatient, to provide somatosensory electrical stimulation to locationsother than the brain, or to deliver a drug or other therapeutic agent(either alone or in conjunction with stimulation).

Also in the implantable neurostimulator device 310 is a memory subsystem526 and the CPU 528, which can take the form of a microcontroller. Thememory subsystem is coupled to the detection subsystem 522 (e.g., forreceiving and storing data representative of sensed EEG signals andevoked responses), the stimulation subsystem 524 (e.g., for providingstimulation waveform parameters to the stimulation subsystem), and theCPU 528, which can control the operation of (and store and retrieve datafrom) the memory subsystem 526. In addition to the memory subsystem 526,the CPU 528 is also connected to the detection subsystem 522 and thestimulation subsystem 524 for direct control of those subsystems.

Also provided in the implantable neurostimulator device 310, and coupledto the memory subsystem 526 and the CPU 528, is a communicationsubsystem 530. The communication subsystem 530 enables communicationbetween the device 310 and the outside world, particularly an externalprogrammer and a patient initiating device, both of which will bedescribed below with reference to FIG. 6. As set forth above, thedisclosed embodiment of the communication subsystem 530 includes atelemetry coil (which may be situated outside of the housing of theimplantable neurostimulator device 310) enabling transmission andreception of signals, to or from an external apparatus, via inductivecoupling. Alternative embodiments of the communication subsystem 530could use an antenna for an RF link or an audio transducer for an audiolink. Preferably, the communication subsystem 530 also includes a GMR(giant magnetoresistive effect) sensor to enable receiving simplesignals (namely the placement and removal of a magnet) from a patientinitiating device; this capability can be used to initiate EEG recordingas will be described in further detail below.

If the stimulation subsystem 524 includes the audio capability set forthabove, it may be advantageous for the communication subsystem 530 tocause the audio signal to be generated by the stimulation subsystem 524upon receipt of an appropriate indication from the patient initiatingdevice (e.g., the magnet used to communicate with the GMR sensor of thecommunication subsystem 530), thereby confirming to the patient orcaregiver that a desired action will be performed, e.g. that an EEGrecord will be stored.

Rounding out the subsystems in the implantable neurostimulator device310 are a power supply 532 and a clock supply 534. The power supply 532supplies the voltages and currents necessary for each of the othersubsystems. The clock supply 534 supplies substantially all of the othersubsystems with any clock and timing signals necessary for theiroperation, including a real-time clock signal to coordinate programmedand scheduled actions and the timer functionality used by the detectionsubsystem 522 that is described in detail below.

It should be observed that while the memory subsystem 526 is illustratedin FIG. 5 as a separate functional subsystem, the other subsystems mayalso require various amounts of memory to perform the functionsdescribed above and others. Furthermore, while the implantableneurostimulator device 310 is preferably a single physical unit (i.e., acontrol module) contained within a single implantable physicalenclosure, namely the housing described above, other embodiments of theinvention might be configured differently. The neurostimulator 310 maybe provided as an external unit not adapted for implantation, or it maycomprise a plurality of spatially separate units each performing asubset of the capabilities described above, some or all of which mightbe external devices not suitable for implantation. Also, it should benoted that the various functions and capabilities of the subsystemsdescribed above may be performed by electronic hardware, computersoftware (or firmware), or a combination thereof. The division of workbetween the CPU 528 and the other functional subsystems may alsovary—the functional distinctions illustrated in FIG. 5 may not reflectthe partitioning and integration of functions in a real-world system ormethod according to the invention.

As stated above, and as illustrated in FIG. 6, a neurostimulatoraccording to the invention operates in conjunction with externalequipment. The implantable neurostimulator device 310 is mostlyautonomous (particularly when performing its usual sensing, detection,and stimulation capabilities), but preferably includes a selectablepart-time wireless link 610 to external equipment such as a programmer612. In the disclosed embodiment of the invention, the wireless link 610is established by moving a wand (or other apparatus) havingcommunication capabilities and coupled to the programmer 612 intocommunication range of the implantable neurostimulator device 310. Theprogrammer 612 can then be used to manually control the operation of thedevice, as well as to transmit information to or receive informationfrom the implantable neurostimulator 310. Several specific capabilitiesand operations performed by the programmer 612 in conjunction with thedevice will be described in further detail below.

The programmer 612 is capable of performing a number of advantageousoperations in connection with the invention. In particular, theprogrammer 612 is able to specify and set variable parameters in theimplantable neurostimulator device 310 to adapt the function of thedevice to meet the patient's needs, upload or receive data (includingbut not limited to stored EEG waveforms, parameters, or logs of actionstaken) from the implantable neurostimulator 310 to the programmer 612,download or transmit program code and other information from theprogrammer 612 to the implantable neurostimulator 310, or command theimplantable neurostimulator 310 to perform specific actions or changemodes as desired by a physician operating the programmer 612. Tofacilitate these functions, the programmer 612 is adapted to receiveclinician input 614 and provide clinician output 616; data istransmitted between the programmer 612 and the implantableneurostimulator 310 over the wireless link 610.

The programmer 612 may be used at a location remote from the implantableneurostimulator 310 if the wireless link 610 is enabled to transmit dataover long distances. For example, the wireless link 610 may beestablished by a short-distance first link between the implantableneurostimulator 310 and a transceiver, with the transceiver enabled torelay communications over long distances to a remote programmer 612,either wirelessly (for example, over a wireless computer network) or viaa wired communications link (such as a telephonic circuit or a computernetwork).

The programmer 612 may also be coupled via a communication link 618 to anetwork 620 such as the Internet. This allows any information uploadedfrom the implantable neurostimulator 310, as well as any program code orother information to be downloaded to the implantable neurostimulator310, to be stored in a database 622 at one or more data repositorylocations (which may include various servers and network-connectedprogrammers like the programmer 612). This would allow a patient (andthe patient's physician) to have access to important data, includingpast treatment information and software updates, essentially anywhere inthe world where there is a programmer (like the programmer 612) and anetwork connection. Alternatively, the programmer 612 may be connectedto the database 622 over a trans-telephonic link.

In yet another alternative embodiment of the invention, the wirelesslink 610 from the implantable neurostimulator 310 may enable a transferof data from the neurostimulator 310 to the database 622 without anyinvolvement by the programmer 612. In this embodiment, as with others,the wireless link 610 may be established by a short-distance first linkbetween the implantable neurostimulator 310 and a transceiver, with thetransceiver enabled to relay communications over long distances to thedatabase 622, either wirelessly (for example, over a wireless computernetwork) or via a wired communications link (such astrans-telephonically over a telephonic circuit, or over a computernetwork).

In the disclosed embodiment, the implantable neurostimulator 310 is alsoadapted to receive communications from an initiating device 624,typically controlled by the patient or a caregiver. Accordingly, patientinput 626 from the initiating device 624 is transmitted over a wirelesslink to the implantable neurostimulator 310; such patient input 626 maybe used to cause the implantable neurostimulator 310 to switch modes (onto off and vice versa, for example) or perform an action (e.g., store arecord of EEG data). Preferably, the initiating device 624 is able tocommunicate with the implantable neurostimulator 310 through thecommunication subsystem 530 (FIG. 5), and possibly in the same mannerthe programmer 612 does. The link may be unidirectional (as with themagnet and GMR sensor described above), allowing commands to be passedin a single direction from the initiating device 624 to the implantableneurostimulator 310, but in an alternative embodiment of the inventionis bi-directional, allowing status and data to be passed back to theinitiating device 624. Accordingly, the initiating device 624 may be aprogrammable PDA or other hand-held computing device, such as a PalmPilot® or PocketPC®. However, a simple form of initiating device 624 maytake the form of a permanent magnet, if the communication subsystem 530is adapted to identify magnetic fields and interruptions therein ascommunication signals.

The implantable neurostimulator 310 (FIG. 3) generally interacts withthe programmer 612 (FIG. 6) as described below. Data stored in thememory subsystem 526 can be retrieved by the patient's physician throughthe wireless communication link 610, which operates through thecommunication subsystem 530 of the implantable neurostimulator 310. Inconnection with the invention, a software operating program run by theprogrammer 612 allows the physician to read out a history ofneurological events detected including EEG information before, during,and after each neurological event, as well as specific informationrelating to the detection of each neurological event (such as, in oneembodiment, the time-evolving energy spectrum of the patient's EEG). Theprogrammer 612 also allows the physician to specify or alter anyprogrammable parameters of the implantable neurostimulator 310. Thesoftware operating program also includes tools for the analysis andprocessing of recorded EEG records to assist the physician in developingoptimized seizure detection parameters for each specific patient.

In an embodiment of the invention, the programmer 612 is primarily acommercially available PC, laptop computer, or workstation having a CPU,keyboard, mouse and display, and running a standard operating systemsuch as Microsoft Windows®, Linux®, Unix®, or Apple Mac OS®. It is alsoenvisioned that a dedicated programmer apparatus with a custom softwarepackage (which may not use a standard operating system) could bedeveloped.

When running the computer workstation software operating program, theprogrammer 612 can process, store, play back and display on the displaythe patient's EEG signals, as previously stored by the implantableneurostimulator 310 of the implantable neurostimulator device.

The computer workstation software operating program also has thecapability to simulate the detection and prediction of epileptiformactivity. Furthermore, the software operating program of the presentinvention has the capability to allow a clinician to create or modify apatient-specific collection of information comprising, in oneembodiment, algorithms and algorithm parameters for epileptiformactivity detection. The patient-specific collection of detectionalgorithms and parameters used for neurological activity detectionaccording to the invention will be referred to herein as a detectiontemplate or patient-specific template. The patient-specific template, inconjunction with other information and parameters generally transferredfrom the programmer to the implanted device (such as stimulationparameters, time schedules, and other patient-specific information),make up a set of operational parameters for the neurostimulator.

Following the development of a patient specific template on theprogrammer 612, the patient-specific template would be downloadedthrough the communications link 610 from the programmer 612 to theimplantable neurostimulator 310.

The patient-specific template is used by the detection subsystem 522 andthe CPU 528 of the implantable neurostimulator 310 to detectepileptiform activity in the patient's EEG signals, which can beprogrammed by a clinician to result in responsive stimulation of thepatient's brain, as well as the storage of EEG records before and afterthe detection, facilitating later clinician review.

Preferably, the database 622 is adapted to communicate over the network620 with multiple programmers, including the programmer 612 andadditional programmers 628, 630, and 632. It is contemplated thatprogrammers will be located at various medical facilities andphysicians' offices at widely distributed locations. Accordingly, ifmore than one programmer has been used to upload EEG records from apatient's implantable neurostimulator 310, the EEG records will beaggregated via the database 622 and available thereafter to any of theprogrammers connected to the network 620, including the programmer 612.

FIG. 7 illustrates details of the detection subsystem 722 (FIG. 7).Inputs from the electrodes 412-418 are on the left, and connections toother subsystems are on the right.

Signals received from the electrodes 512-518 (as routed through theelectrode interface 520) are received in an electrode selector 710. Theelectrode selector 710 allows the device to select which electrodes (ofthe electrodes 512-518) should be routed to which individual sensingchannels of the detection subsystem 522, based on commands receivedthrough a control interface 718 from the memory subsystem 526 or the CPU528 (FIG. 5). Preferably, each sensing channel of the detectionsubsystem 522 receives a bipolar signal representative of the differencein electrical potential between two selectable electrodes. Accordingly,the electrode selector 710 provides signals corresponding to each pairof selected electrodes (of the electrodes 512-518) to a sensing frontend 712, which performs amplification, analog to digital conversion, andmultiplexing functions on the signals in the sensing channels. Thesensing front end will be described further below in connection withFIG. 8.

A multiplexed input signal representative of all active sensing channelsis then fed from the sensing front end 712 to a waveform analyzer 714.The waveform analyzer 714 is preferably a special-purpose digital signalprocessor (DSP) adapted for use with the invention, or in an alternativeembodiment, may comprise a programmable general-purpose DSP. In thedisclosed embodiment, the waveform analyzer has its own scratchpadmemory area 716 used for local storage of data and program variableswhen the signal processing is being performed. In either case, thesignal processor performs suitable measurement and detection methodsdescribed generally above and in greater detail below. Any results fromsuch methods, as well as any digitized signals intended for storagetransmission to external equipment, are passed to various othersubsystems of the device 310, including the memory subsystem 526 and theCPU 528 (FIG. 5) through a data interface 720. Similarly, the controlinterface 718 allows the waveform analyzer 714 and the electrodeselector 710 to be in communication with the CPU 528.

Referring now to FIG. 8, the sensing front end 712 (FIG. 7) isillustrated in further detail. As shown, the sensing front end includesa plurality of differential amplifier channels 810, each of whichreceives a selected pair of inputs from the electrode selector 710. In apreferred embodiment of the invention, each of differential amplifierchannels 810 is adapted to receive or to share inputs with one or moreother differential amplifier channels 810 without adversely affectingthe sensing and detection capabilities of a system according to theinvention. Specifically, in an embodiment of the invention, there are atleast eight electrodes, which can be mapped separately to eightdifferential amplifier channels 810 representing eight different sensingchannels and capable of individually processing eight bipolar signals,each of which represents an electrical potential difference between twomonopolar input signals received from the electrodes and applied to thesensing channels via the electrode selector 710. For clarity, only fivechannels are illustrated in FIG. 8, but it should be noted that anypractical number of sensing channels may be employed in a systemaccording to the invention.

Each differential amplifier channel 810 feeds a corresponding analog todigital converter (ADC) 812. Preferably, the analog to digitalconverters 812 are separately programmable with respect to samplerates—in the disclosed embodiment, the ADCs 812 convert analog signalsinto 10-bit unsigned integer digital data streams at a sample rateselectable between 250 Hz and 500 Hz. In several of the illustrationsdescribed below where waveforms are shown, sample rates of 250 Hz aretypically used for simplicity. However, the invention shall not bedeemed to be so limited, and numerous sample rate and resolution optionsare possible, with tradeoffs known to individuals of ordinary skill inthe art of electronic signal processing. The resulting digital signalsare received by a multiplexer 814 that creates a single interleaveddigital data stream representative of the data from all active sensingchannels. As will be described in further detail below, not all of thesensing channels need to be used at one time, and it may in fact beadvantageous in certain circumstances to deactivate certain sensingchannels to reduce the power consumed by a system according to theinvention.

It should be noted that as illustrated and described herein, a “sensingchannel” is not necessarily a single physical or functional item thatcan be identified in any illustration. Rather, a sensing channel isformed from the functional sequence of operations described herein, andparticularly represents a single electrical signal received from anypair or combination of electrodes, as preprocessed by a system accordingto the invention, in both analog and digital forms. See, e.g., U.S.patent application Ser. No. 09/517,797 to D. Fischell et al., filed onMar. 2, 2000 and entitled “neurological Event Detection Using ProcessedDisplay Channel Based Algorithms and Devices Incorporating TheseProcedures,” which is hereby incorporated by reference as though setforth in full herein. At times (particularly after the multiplexer 814),multiple sensing channels are processed by the same physical andfunctional components of the system; notwithstanding that, it should berecognized that unless the description herein indicates to the contrary,a system according to the invention processes, handles, and treats eachsensing channel independently.

The interleaved digital data stream is passed from the multiplexer 814,out of the sensing front end 712, and into the waveform analyzer 714.The waveform analyzer 714 is illustrated in detail in FIG. 9.

The interleaved digital data stream representing information from all ofthe active sensing channels is first received by a channel controller910. The channel controller applies information from the active sensingchannels to a number of wave morphology analysis units 912 and windowanalysis units 914. It is preferred to have as many wave morphologyanalysis units 912 and window analysis units 914 as possible, consistentwith the goals of efficiency, size, and low power consumption necessaryfor an implantable device. In a presently preferred embodiment of theinvention, there are sixteen wave morphology analysis units 912 andeight window analysis units 914, each of which can receive data from anyof the sensing channels of the sensing front end 712 (FIG. 7), and eachof which can be operated with different and independent parameters,including differing sample rates, as will be discussed in further detailbelow.

Each of the wave morphology analysis units 912 operates to extractcertain feature information from an input waveform as described below inconjunction with FIGS. 12-15. Similarly, each of the window analysisunits 914 performs certain data reduction and signal analysis withintime windows in the manner described in conjunction with FIGS. 16-21.Output data from the various wave morphology analysis units 912 andwindow analysis units 914 are combined via event detector logic 916. Theevent detector logic 916 and the channel controller 910 are controlledby control commands 918 received from the control interface 718 (FIG.7).

A “detection channel,” as the term is used herein, refers to a datastream including the active sensing front end 712 and the analysis unitsof the waveform analyzer 714 processing that data stream, in both analogand digital forms. It should be noted that each detection channel canreceive data from a single sensing channel; each sensing channelpreferably can be applied to the input of any combination of detectionchannels. The latter selection is accomplished by the channel controller910. As with the sensing channels, not all detection channels need to beactive; certain detection channels can be deactivated to save power orif additional detection processing is deemed unnecessary in certainapplications.

In conjunction with the operation of the wave morphology analysis units912 and the window analysis units 914, a scratchpad memory area 716 isprovided for temporary storage of processed data. The scratchpad memoryarea 716 may be physically part of the memory subsystem 526 (FIG. 5), oralternatively may be provided for the exclusive use of the waveformanalyzer 714 (FIG. 7). Other subsystems and components of a systemaccording to the invention may also be furnished with local scratchpadmemory, if such a configuration is advantageous.

The operation of the event detector logic 916 is illustrated in detailin the functional block diagram of FIG. 10, in which four exemplarysensing channels are analyzed by three illustrative signal eventdetectors.

A first sensing channel 1010 provides input to a first event detector1012. While the first event detector 1012 is illustrated as a functionalblock in the block diagram of FIG. 10, it should be recognized that itis a functional block only for purposes of illustration, and may nothave any physical counterpart in a device according to the invention.Similarly, a second sensing channel 1014 provides input to a secondevent detector 1016, and a third input channel 1018 and a fourth inputchannel 1020 both provide input to a third event detector 1022.

Considering the processing performed by the event detectors 1012, 1016,and 1022, the first input channel 1010 feeds a signal to both a wavemorphology analysis unit 1024 (one of the wave morphology analysis units912 of FIG. 9) and a window analysis unit 1026 (one of the windowanalysis units 914 of FIG. 9). The window analysis unit 1026, in turn,includes a line length analysis tool 1028 and an area analysis tool1030. As will be discussed in detail below, the line length analysistool 1028 and the area analysis tool 1030 analyze different aspects ofthe signal from the first input channel 1010.

Outputs from the wave morphology analysis unit 1024, the line lengthanalysis tool 1028, and the area analysis tool 1030 are combined in aBoolean AND operation 1032 and sent to an output 1034 for further use bya system according to the invention. For example, if a combination ofanalysis tools in an event detector identifies several simultaneous (ornear-simultaneous) types of activity in an input channel, a systemaccording to the invention may be programmed to perform an action inresponse thereto. Details of the analysis tools and the combinationprocesses used in event detectors according to the invention will be setforth in greater detail below.

In the second event detector 1016, only a wave morphology analysis unit1036 is active. Accordingly, no Boolean operation needs to be performed,and the wave morphology analysis unit 1036 directly feeds an eventdetector output 1038.

The third event detector 1022 operates on two input channels 1018 and1020, and includes two separate detection channels of analysis units: afirst wave morphology analysis unit 1040 and a first window analysisunit 1042, the latter including a first line length analysis tool 1044and a first area analysis tool 1046; and a second wave morphologyanalysis unit 1048 and a second window analysis unit 1050, the latterincluding a second line length analysis tool 1052 and a second areaanalysis tool 1054. The two detection channels of analysis units arecombined to provide a single event detector output 1056.

In the first detection channel of analysis units 1040 and 1042, outputsfrom the first wave morphology analysis unit 1040, the first line lengthanalysis tool 1044, and the first area analysis tool 1046 are combinedvia a Boolean AND operation 1058 into a first detection channel output1060. Similarly, in the second detection channel of analysis units 1048and 1050, outputs from the second wave morphology analysis unit 1048,the second line length analysis tool 1052, and the second area analysistool 1054 are combined via a Boolean AND operation 1062 into a seconddetection channel output 1064. In the illustrated embodiment of theinvention, the second detection channel output 1064 is invertible withselectable Boolean logic inversion 1066 before it is combined with thefirst detection channel output 1060. Subsequently, the first detectionchannel output 1060 and the second detection channel output 1064 arecombined with a Boolean AND operation 1068 to provide a signal to theoutput 1056. In an alternative embodiment, a Boolean OR operation isused to combine the first detection channel output 1060 and the seconddetection channel output 1064.

In one embodiment of the invention, the second detection channel(analysis units 1048 and 1050) represents a “qualifying channel” withrespect to the first detection channel (analysis units 1040 and 1042).In general, a qualifying channel allows a detection to be made only whenboth channels are in concurrence with regard to detection of a signalevent. For example, a qualifying channel can be used to indicate when aseizure has “generalized,” i.e. spread through a significant portion ofa patient's brain. To do this, the third input channel 1018 and thefourth input channel 1020 are configured to receive EEG waveforms fromseparate amplifier channels coupled to electrodes in separate parts ofthe patient's brain (e.g., in opposite hemispheres). Accordingly, then,the Boolean AND operation 1068 will indicate a detection only when thefirst detection output 1060 and the second detection output 1064 bothindicate the presence of an signal event (or, when Boolean logicinversion 1066 is present, when the first detection output 1060indicates the presence of a signal event while the second detectionoutput 1064 does not). As will be described in further detail below, thedetection outputs 1060 and 1064 can be provided with selectablepersistence (i.e., the ability to remain triggered for some time afterthe signal event is detected), allowing the Boolean AND combination 1068to be satisfied even when there is not precise temporal synchronizationbetween detections on the two channels.

It should be appreciated that the concept of a “qualifying channel”allows the flexible configuration of a device 310 according to theinvention to achieve a number of advantageous results. In addition tothe detection of generalization, as described above, a qualifyingchannel can be configured, for example, to detect noise so a detectionoutput is valid only when noise is not present, to assist in deviceconfiguration in determining which of two sets of detection parametersis preferable (by setting up the different parameters in the firstdetection channel and the second detection channel, then replacing theBoolean AND combination with a Boolean OR combination), or to require aspecific temporal sequence of detections (which would be achieved insoftware by the CPU 528 after a Boolean OR combination of detections).Moreover, a qualifying channel can receive data from the same inputchannel as the first detection channel, allowing the correlation ofseparate pattern characteristics occurring at the same time in the samewaveform. There are numerous other possibilities.

The outputs 1034, 1038, and 1056 of the event detectors are preferablyrepresented by Boolean flags, and as described below, provideinformation for the operation of a system according to the invention.

While FIG. 10 illustrates four different sensing channels providinginput to four separate detection channels, it should be noted that amaximally flexible embodiment of the present invention would allow eachsensing channel to be connected to one or more detection channels. Itmay be advantageous to program the different detection channels withdifferent settings (e.g., thresholds) to facilitate alternate “views” ofthe same sensing channel data stream.

FIG. 11 illustrates three representative waveforms of the type expectedto be manipulated by a system according to the invention. It should benoted, however, that the waveforms illustrated in FIG. 11 areillustrative only, and are not intended to represent any actual data.The first waveform 1110 is representative of an unprocessedelectroencephalogram (EEG) or electrocorticogram (ECOG) waveform havinga substantial amount of variability; the illustrated segment has aduration of approximately 160 ms and a dominant frequency (visible asthe large-scale crests and valleys) of approximately 12.5 Hz. It will berecognized that the first waveform is rather rough and peaky; there is asubstantial amount of high-frequency energy represented therein.

The second waveform 1112 represents a filtered version of the originalEEG waveform 1110. As shown, most of the high-frequency energy has beeneliminated from the signal, and the waveform 1112 is significantlysmoother. In the disclosed embodiment of the invention, this filteringoperation is performed in the sensing front end 712 (FIG. 7) before theanalog to digital converters 812 (FIG. 8).

The filtered waveform 1112 is then sampled by one of the analog todigital converters 812; this operation is represented graphically in thethird waveform 1114 of FIG. 11. As illustrated, a sample rate used in anembodiment of the invention is 250 Hz (4 ms sample duration), resultingin approximately 40 samples over the illustrated 160 ms segment. As iswell known in the art of digital signal processing, the amplituderesolution of each sample is limited; in the disclosed embodiment, eachsample is measured with a resolution of 10 bits (or 1024 possiblevalues). As is apparent upon visual analysis of the third waveform, thedominant frequency component has a wavelength of approximately 20samples, which corresponds to the dominant frequency of 12.5 Hz.

Referring now to FIG. 12, the processing of the wave morphology analysisunits 912 is described in conjunction with a filtered and sampledwaveform 1114 of the type illustrated as the third waveform 1114 of FIG.11.

In a first half wave 1212, which is partially illustrated in FIG. 12(the starting point occurs before the illustrated waveform segment 1114begins), the waveform segment 1114 is essentially monotonicallydecreasing, except for a small first perturbation 1214. Accordingly, thefirst half wave 1212 is represented by a vector from the starting point(not shown) to a first local extremum 1216, where the waveform starts tomove in the opposite direction. The first perturbation 1214 is ofinsufficient amplitude to be considered a local extremum, and isdisregarded by a hysteresis mechanism (discussed in further detailbelow). A second half wave 1218 extends between the first local extremum1216 and a second local extremum 1220. Again, a second perturbation 1222is of insufficient amplitude to be considered an extremum. Likewise, athird half wave 1224 extends between the second local extremum 1220 anda third local extremum 1226; this may appear to be a small perturbation,but is greater in amplitude than a selected hysteresis threshold. Theremaining half waves 1228, 1230, 1232, 1234, and 1236 are identifiedanalogously. As will be discussed in further detail below, each of theidentified half waves 1212, 1218, 1224, 1228, 1230, 1232, 1234, and 1236has a corresponding duration 1238, 1240, 1242, 1244, 1246, 1248, 1250,and 1252, respectively, and analogously, a corresponding amplitudedetermined from the relative positions of each half wave's startingpoint and ending point along the vertical axis, and a slope direction,increasing or decreasing.

In a method performed according to the invention, it is particularlyadvantageous to allow for a programmable hysteresis setting inidentifying the ends of half waves. In other words, as explained above,the end of an increasing or decreasing half wave might be prematurelyidentified as a result of quantization (and other) noise, low-amplitudesignal components, and other perturbing factors, unless a smallhysteresis allowance is made before a reversal of waveform direction(and a corresponding half wave end) is identified. Hysteresis allows forinsignificant variations in signal level inconsistent with the signal'soverall movement to be ignored without the need for extensive furthersignal processing such as filtering. Without hysteresis, such small andinsignificant variations might lead to substantial and gross changes inwhere half waves are identified, leading to unpredictable results.

The processing steps performed with regard to the waveform 1114 and halfwaves of FIG. 12 are set forth in FIG. 13. The method begins byidentifying an increasing half wave (with an ending amplitude higherthan the starting amplitude, as in the second half wave 1218 of FIG.12). To do this, a variable corresponding to half wave time is firstinitialized to zero (step 1310); then half wave duration, endingthreshold, peak amplitude, and first sample value are all initialized(step 1312). Specifically, the half wave duration value is set to zero;the peak amplitude and first sample values are set to the amplitudevalue of the last observed sample, which as described above is a valuehaving 10-bit precision; and the ending threshold is set to the lastobserved sample minus a small preset hysteresis value. After waiting fora measurement of the current EEG sample (step 1314), the half wave timeand half wave duration variables are incremented (step 1316). If thecurrent EEG sample has an amplitude greater than the peak amplitude(step 1318), then the amplitude of the half wave is increasing (orcontinues to increase). Accordingly, the ending threshold is reset to bethe current EEG sample's amplitude minus the hysteresis value, and thepeak is reset to the current EEG sample's amplitude (step 1320), and thenext sample is awaited (step 1314).

If the current EEG sample has an amplitude less than the endingthreshold (step 1322), then the hysteresis value has been exceeded, anda local extremum has been identified. Accordingly, the end of theincreasing half wave has been reached, and the amplitude and duration ofthe half wave are calculated (step 1324). The amplitude is equal to thepeak amplitude minus the first sample value; the duration is equal tothe current half wave duration. Otherwise, the next ample is awaited(step 1314).

If both the amplitude and the duration qualify by exceedingcorresponding preset thresholds (step 1326), then the amplitude,duration, half wave time, half wave direction (increasing) are stored ina buffer (step 1328), and the half wave time is reset to zero (step1330).

At the conclusion of the increasing half wave, the process continues byinitializing wave duration, the ending threshold, the peak amplitude,and the first sample value (step 1332). Wave duration is set to zero,the ending threshold is set to the last sample value plus the hysteresisvalue, the peak amplitude and the first sample value are set to the mostrecent sample value.

After waiting for a measurement of the current EEG sample (step 1334),the half wave time and half wave duration variables are incremented(step 1336). If the current EEG sample has an amplitude lower than thepeak amplitude (step 1338), then the amplitude of the half wave isdecreasing (or continues to decrease). Accordingly, the ending thresholdis reset to be the current EEG sample's amplitude plus the hysteresisvalue, the peak is reset to the current EEG sample's amplitude (step1340), and the next sample is awaited (step 1334).

If the current EEG sample has an amplitude greater than the endingthreshold (step 1342), then the hysteresis value has been exceeded, anda local extremum has been identified. Accordingly, the end of thedecreasing half wave has been reached, and the amplitude and duration ofthe half wave are calculated (step 1344). The amplitude is equal to thefirst sample value minus the peak amplitude, and the duration is equalto the current half wave duration. Otherwise, the next EEG sample isawaited (step 1334).

If both the amplitude and the duration qualify by exceedingcorresponding preset thresholds (step 1346), then the amplitude,duration, half wave time, half wave direction (decreasing) are stored ina buffer (step 1348), and the half wave time is reset to zero (step1350). It should be noted that, in the context of this specification,the term “exceed” in regard to a threshold value means to meet aspecified criterion. Generally, to exceed a threshold herein is to havea numeric value greater than or equal to the threshold, although otherinterpretations (such as greater than, or less than, or less than orequal to, depending on the context) may be applicable and are deemed tobe within the scope of the invention.

At the conclusion of the decreasing half wave, further half waves arethen identified by repeating the process from step 1312. As half wavedetection is an ongoing and continuous process, this procedurepreferably does not exit, but may be suspended from time to time whenconditions or device state call for it, e.g. when the device is inactiveor when stimulation is being performed. Once suspended in accordancewith the invention, the procedure should recommence with the firstinitialization step 1310.

Accordingly, the process depicted in FIG. 13 stores parameterscorresponding to qualified half waves, including their directions,durations, amplitudes, and the elapsed time between adjacent qualifiedhalf waves (i.e. the half wave time variable). In the disclosedembodiment of the invention, to reduce power consumption, this procedureis performed in custom electronic hardware; it should be clear that theoperations of FIG. 13 are performed in parallel for each active instanceof the wave morphology analysis units 912 (FIG. 9). It should also benoted, however, that certain software can also be used to advantageouseffect in this context.

This stored information is used in the software process illustrated inFIG. 14, which is performed on a periodic basis, preferably once everyprocessing window (a recurring time interval that is either fixed orprogrammable) by a system according to the invention. Consistent withthe other analysis tools described herein, the duration of an exemplaryprocessing window is in one embodiment of the invention 128 ms, whichcorresponds to 32 samples at a 250 Hz sampling rate.

Each time the software process of FIG. 14 is invoked, the half wavewindow flag is first cleared (step 1410). Any qualified half wavesidentified by the process set forth in FIG. 13 that are newly identifiedsince the last invocation of the procedure (i.e., all qualified halfwaves that ended within the preceding processing window) are identified(step 1412). A “current half wave” pointer is set to point to the oldestqualified half wave identified in the most recent processing window(step 1414). The time interval between the current half wave and theprior x half waves is then measured (step 1416), where x is a specifiedminimum number of half waves (preferably a programmable value) to beidentified within a selected half wave time window (the duration ofwhich is another programmable value) to result in the possible detectionof a neurological event. If the time interval is less than the durationof the half wave time window (step 1418), then the half wave window flagis set (step 1420), logic inversion is selectively applied (step 1422),and the procedure ends (step 1424). Logic inversion, a mechanism fordetermining whether an analysis unit is triggered by the presence orabsence of a condition, is explained in greater detail below. Otherwise,the current half wave pointer is incremented to point to the next newhalf wave (step 1428), and if there are no more new half waves (step1430), logic inversion is applied if desired (step 1422), and theprocedure ends (step 1424). Otherwise, the next time interval is tested(step 1416) and the process continues from there.

Logic inversion allows the output flag for the wave morphology analysisunit (or any other analyzer) to be selectively inverted. If logicinversion is configured to be applied to an output of a particularanalysis unit, then the corresponding flag will be clear when thedetection criterion (e.g., number of qualified half waves) is met, andset when the detection criterion is not met. This capability providessome additional flexibility in configuration, facilitating detection ofthe absence of certain signal characteristics when, for example, thepresence of those characteristics is the norm.

In a preferred embodiment of the invention, the half wave window flag(set in step 1420) indicates whether a sufficient number of qualifiedhalf waves occur over an interval ending in the most recent processingwindow. To reduce the occurrence of spurious detections, an X of Ycriterion is applied, causing the wave morphology analysis unit totrigger only if a sufficient number of qualified half waves occur in Xof the Y most recent processing windows, where X and Y are parametersindividually adjustable for each analysis tool. This process isillustrated in FIG. 15.

Initially, a sun (representing recent processing windows having the halfwave window flag set) is cleared to zero and a current window pointer isinitialized to point to the most recent processing window (step 1510).If the half wave window flag corresponding to the current window pointeris set (step 1512), then the sum is incremented (step 1514). If thereare more processing windows to examine (for an X of Y criterion, a totalof Y processing windows, including the most recent, should beconsidered) (step 1516), then the window pointer is decremented (step1518) and the flag testing and sum incrementing steps (steps 1512-1314)are repeated.

After Y windows have been considered, if the sum of windows having sethalf wave window flags meets the threshold X (step 1520), then the halfwave analysis flag is set (step 1522), persistence (described below) isapplied (step 1524), and the procedure is complete. Otherwise, the halfwave analysis flag is cleared (step 1526).

Persistence, another per-analysis-tool setting, allows the effect of asignal event detection (a flag set) to persist beyond the end of thedetection window in which the signal event occurs. In the disclosedsystem according to the invention, persistence may be set anywhere fromone second to fifteen seconds (though other settings are possible), soif detections with multiple analysis tools do not all occursimultaneously (though they should still occur within a fairly shorttime period), a Boolean combination of flags will still yield positiveresults. Persistence can also be used with a single analysis tool tosmooth the results.

When the process of FIG. 15 is completed, the half wave analysis flag(set or cleared in steps 1522 and 1526, respectively) indicates whethera signal event has been detected in the corresponding channel of thewave morphology analysis units 912, or stated another way, whether asufficient number of qualified half waves have appeared in X of the Ymost recent processing windows. Although in the disclosed embodiment,the steps of FIGS. 14 and 15 are performed in software, it should berecognized that some or all of those steps can be performed using customelectronics, if it proves advantageous in the desired application to usesuch a configuration.

FIG. 16 illustrates the waveform 1114 of FIG. 11, further depicting linelengths identified within a time window. The time window used withrespect to FIGS. 16-18 may be different from the half wave processingwindow described above in connection with FIGS. 14-15, but in apreferred embodiment, refers to the same time intervals. From animplementation standpoint, a single device interrupt upon the conclusionof each processing window allows all of the analysis tools to performthe necessary corresponding software processes; the line length analysisprocess of FIG. 16 (described below) is one such example. The waveform1114 is a filtered and otherwise pre-processed EEG signal as received inone of the window analysis units 914 from the sensing front end 712. Asdiscussed above, line lengths are considered within time windows. Asillustrated in FIG. 16, the duration of an exemplary window 1612 is 32samples, which is equivalent to 128 ms at a 250 Hz sampling rate.

The total line length for the window 1612 is the sum of thesample-to-sample amplitude differences within that window 1612. Forexample, the first contribution to the line length within the window1612 is a first amplitude difference 1614 between a previous sample 1616occurring immediately before the window 1612 and a first sample 1618occurring within the window 1612. The next contribution comes from asecond amplitude difference 1620 between the first sample 1618 and asecond sample 1622; a further contribution 1624 comes from a thirdamplitude difference between the second sample 1622 and a third sample1626; and so on. At the end of the window 1612, the final contributionto the line length comes from a last amplitude difference 1630 between asecond-last sample 1632 in the window 1612 and a last sample 1634 in thewindow 1612. Note that all line lengths, whether increasing ordecreasing in direction, are accumulated as positive values by theinvention; accordingly, a decreasing amplitude difference 1614 and anincreasing amplitude difference 1628 both contribute to a greater linelength.

As illustrated herein, and as discussed in detail above, there arethirty-two samples within the window 1612. As stated above, theillustrated window 1612 has a duration of 128 ms, and accordingly, theillustrated sample rate is 250 Hz. It should be noted, however, thatalternate window durations and sample rates are possible and consideredto be within the scope of the present invention.

The line lengths illustrated in FIG. 16 are calculated as shown by theflow chart of FIG. 17, which is invoked at the beginning of a timewindow. Initially, a line length total variable is initialized to zero(step 1710). The current sample is awaited (step 1712), and the absolutevalue of the amplitude difference between the current sample and theprevious sample (which, when considering the first sample in a window,may come from the last sample in a previous window) is measured (step1714).

In various alternative embodiments of the invention, either the measureddifference (as calculated in step 1714, described above), or the samplevalues used to calculate the difference may be mathematicallytransformed in useful nonlinear ways. For example, it may beadvantageous in certain circumstances to calculate the differencebetween adjacent samples using the squares of the sample values, or tocalculate the square of the difference between sample values, or both.It is contemplated that other transformations (such as square root,exponentiation, logarithm, and other nonlinear functions) might also beadvantageous in certain circumstances. Whether or not to perform such atransformation and the nature of any transformation to be performed arepreferably programmable parameters of the device 310.

For use in the next iteration, the previous sample is replaced with thevalue of the current sample (step 1716), and the calculated absolutevalue is added to the total (step 1718). If there are more samplesremaining in the window 1412 (step 1720), another current sample isawaited (step 1712) and the process continues. Otherwise, the linelength calculation for the window 1412 is complete, and the total isstored (step 1722), the total is re-initialized to zero (step 1710), andthe process continues.

As with the half wave analysis method set forth above, the line lengthcalculation does not need to terminate; it can be free-running yetinterruptible. If the line length calculation is restarted after havingbeen suspended, it should be re-initialized and restarted at thebeginning of a window. This synchronization can be accomplished throughhardware interrupts.

The line lengths calculated as shown in FIG. 17 are then processed asindicated in the flow chart of FIG. 18, which is performed after eachwindow 1612 is calculated and stored (step 1722).

The process begins by calculating a running accumulated line lengthtotal over a period of n time windows. Where n>1, the effect is that ofa sliding window; in an alternative embodiment an actual sliding windowprocessing methodology may be used. First, the accumulated total isinitialized to zero (step 1810). A current window pointer is set toindicate the n^(th)-last window, i.e., the window (n−1) windows beforethe most recent window (step 1812). The line length of the currentwindow is added to the total (step 1814), the current window pointer isincremented (step 1816), and if there are more windows between thecurrent window pointer and the most recent (last) window (step 1818),the adding and incrementing steps (1814-1816) are repeated. Accordingly,by this process, the resulting total includes the line lengths for eachof the n most recent windows.

In the disclosed embodiment of the invention, the accumulated total linelength is compared to a dynamic threshold, which is based on a trend ofrecently observed line lengths. The trend is recalculated regularly andperiodically, after each recurring line length trend interval (which ispreferably a fixed or programmed time interval). Each time the linelength trend interval passes (step 1820), the line length trend iscalculated or updated (step 1822). In a presently preferred embodimentof the invention, this is accomplished by calculating a normalizedmoving average of several trend samples, each of which representsseveral consecutive windows of line lengths. A new trend sample is takenand the moving average is recalculated upon every line length trendinterval. The number of trend samples used in the normalized movingaverage and the number of consecutive windows of line lengthmeasurements per trend sample are preferably both fixed or programmablevalues.

After the line length trend has been calculated, the line lengththreshold is calculated (step 1824) based on the new line length trend.In the disclosed embodiment of the invention, the threshold may be setas either a percentage of the line length trend (either below 100% for athreshold that is lower than the trend, or above 100% for a thresholdthat is higher than the trend) or alternatively a fixed numeric offsetfrom the line length trend (either negative for a threshold that islower than the trend, or positive for a threshold that is higher thanthe trend). It should be observed that other methods for deriving anumeric threshold from a numeric trend are possible and deemed to bewithin the scope of the invention.

The first time the process of FIG. 18 is performed, there is generallyno line length trend against which to set a threshold. Accordingly, forthe first several passes through the process (until a sufficient amountof EEG data has been processed to establish a trend), the threshold isessentially undefined and the line length detector should not return apositive detection. Some “settling time” is required to establish trendsand thresholds before a detection can be made.

If the accumulated line length total exceeds the calculated threshold(step 1826), then a flag is set (step 1828) indicating aline-length-based signal event detection on the current window analysisunit channel 914. As described above, in the disclosed embodiment of theinvention, the threshold is dynamically calculated from a line lengthtrend, but alternatively, the threshold may be static, either fixed orprogrammed into the device 310. If the accumulated line length totaldoes not exceed the threshold, the flag is cleared (step 1830). Once theline length flag has been either set or cleared, logic inversion isapplied (step 1832), persistence is applied (step 1834), and theprocedure terminates.

The resulting persistent line length flag indicates whether thethreshold has been exceeded within one or more windows over a timeperiod corresponding to the line length flag persistence. As will bediscussed in further detail below, line length signal event detectionscan be combined with the half wave signal event detections, as well asany other applicable detection criteria according to the invention.

FIG. 19 illustrates the waveform of FIG. 11 with area under the curveidentified within a window. Area under the curve, which in somecircumstances is somewhat representative of a signal's energy (thoughenergy of a waveform is more accurately represented by the area underthe square of a waveform), is another detection criterion in accordancewith the invention.

The total area under the curve represented by the waveform 1114 withinthe window 1912 is equal to the sum of the absolute values of the areasof each rectangular region of unit width vertically bounded by thehorizontal axis and the sample. For example, the first contribution tothe area under the curve within the window 1912 comes from a firstregion 1914 between a first sample 1916 and a baseline 1917. A secondcontribution to the area under the curve within the window 1912 comesfrom a second region 1918, including areas between a second sample 1920and the baseline 1917. There are similar regions and contributions for athird sample 1922 and the baseline 1917, a fourth sample 1924 and thebaseline 1917, and so on. It should be observed that the region widthsare not important—the area under each sample can be considered theproduct of the sample's amplitude and a unit width, which can bedisregarded. In a similar manner, each region is accumulated and addedto the total area under the curve within the window 1912. Although theconcept of separate rectangular regions is a useful construct forvisualizing the idea of area under a curve, it should be noted that aprocess for calculating area need not partition areas into regions asshown in FIG. 19—it is only necessary to accumulate the absolute valueof the waveform's amplitude at each sample, as the unit width of eachregion can be disregarded. The process for doing this will be set forthin detail below in connection with FIG. 20.

The areas under the curve illustrated in FIG. 19 are calculated as shownby the flow chart of FIG. 20, which is invoked at the beginning of atime window. Initially, an area total variable is initialized to zero(step 2010). The current sample is awaited (step 2012), and the absolutevalue of the current sample is measured (step 2014).

As with the line length calculation method described above (withreference to FIG. 17), in various alternative embodiments of theinvention, the current sample (as measured in step 2014, describedabove) may be mathematically transformed in useful nonlinear ways. Forexample, it may be advantageous in certain circumstances to calculatethe square of the current sample rather than its absolute value. Theresult of such a transformation by squaring each sample will generallybe more representative of signal energy, though it is contemplated thatother transformations (such as square root, exponentiation, logarithm,and other nonlinear functions) might also be advantageous in certaincircumstances. Whether or not to perform such a transformation and thenature of any transformation to be performed are preferably programmableparameters of the device 310.

The calculated absolute value is added to the total (step 2016). Ifthere are more samples remaining in the window 1912 (step 2018), anothercurrent sample is awaited (step 2012) and the process continues.Otherwise, the area calculation for the window 1912 is complete, and thetotal is stored (step 2020), the total is re-initialized to zero (step2010), and the process continues.

As with the half wave and line length analysis methods set forth above,the area calculation does not need to terminate; it can be free-runningyet interruptible. If the area calculation is restarted after havingbeen suspended, it should be re-initialized and restarted at thebeginning of a window. This synchronization can be accomplished throughhardware interrupts.

The line lengths calculated as shown in FIG. 20 are then processed asindicated in the flow chart of FIG. 21, which is performed after eachwindow 1912 is calculated and stored (step 2020).

The process begins by calculating a running accumulated area total overa period of n time windows. Where n>1, the effect is that of a slidingwindow; in an alternative embodiment an actual sliding window processingmethodology may be used. First, the accumulated total is initialized tozero (step 2110). A current window pointer is set to indicate then^(th)-last window, i.e., the window (n−1) windows before the mostrecent window (step 2112). The area for the current window is added tothe total (step 2114), the current window pointer is incremented (step2116), and if there are more windows between the current window and themost recent (last) window (step 2118), the adding and incrementing steps(2114-2116) are repeated. Accordingly, by this process, the resultingtotal includes the areas under the curve for each of the n most recentwindows.

In the disclosed embodiment of the invention, the accumulated total areais compared to a dynamic threshold, which is based on a trend ofrecently observed areas. The trend is recalculated regularly andperiodically, after each recurring area trend interval (which ispreferably a fixed or programmed time interval). Each time the areatrend interval passes (step 2120), the area trend is calculated orupdated (step 2122). In a presently preferred embodiment of theinvention, this is accomplished by calculating a normalized movingaverage of several trend samples, each of which represents severalconsecutive windows of areas. A new trend sample is taken and the movingaverage is recalculated upon every area trend interval. The number oftrend samples used in the normalized moving average and the number ofconsecutive windows of area measurements per trend sample are preferablyboth fixed or programmable values.

After the area trend has been calculated, the area threshold iscalculated (step 2124) based on the new area trend. As with line length,discussed above, the threshold may be set as either a percentage of thearea trend (either below 100% for a threshold that is lower than thetrend, or above 100% for a threshold that is higher than the trend) oralternatively a fixed numeric offset from the area trend (eithernegative for a threshold that is lower than the trend, or positive for athreshold that is higher than the trend).

The first time the process of FIG. 21 is performed, there is generallyno area trend against which to set a threshold. Accordingly, for thefirst several passes through the process (until a sufficient amount ofEEG data has been processed to establish a trend), the threshold isessentially undefined and the area detector should not return a positivedetection. Some “settling time” is required to establish trends andthresholds before a detection can be made.

If the accumulated total exceeds the calculated threshold (step 2126),then a flag is set (step 2128) indicating an area-based signal eventdetection on the current window analysis unit channel 914. Otherwise,the flag is cleared (step 2130). Once the area flag has been either setor cleared, logic inversion is applied (step 2132), persistence isapplied (step 2134), and the procedure terminates.

The resulting persistent area flag indicates whether the threshold hasbeen exceeded within one or more windows over a time periodcorresponding to the area flag persistence. As will be discussed infurther detail below, area signal event detections can be combined withthe half wave signal event detections, line length signal eventdetections, as well as any other applicable detection criteria accordingto the invention.

In a preferred embodiment of the invention, each threshold for eachchannel and each analysis tool can be programmed separately;accordingly, a large number of individual thresholds may be used in asystem according to the invention. It should be noted thresholds canvary widely; they can be updated by a physician via the externalprogrammer 612 (FIG. 6), and some analysis tool thresholds (e.g., linelength and area) can also be automatically varied depending on observedtrends in the data. This is preferably accomplished based on a movingaverage of a specified number of window observations of line length orarea, adjusted as desired via a fixed offset or percentage offset, andmay compensate to some extent for diurnal and other normal variations inbrain electrophysiological parameters.

With regard to the flow charts of FIGS. 13-15, 17-18, and 20-21, itshould be noted that there can be a variety of ways these processes areimplemented. For example, software, hardware (including ASICs, FPGAs,and other custom electronics), and various combinations of software andhardware, are all solutions that would be possible to practitioners ofordinary skill in the art of electronics and systems design. It shouldfurther be noted that the steps described herein as performed insoftware need not be, as some of them can be implemented in hardware, ifdesired, to further reduce computational load on the processor. In thecontext of the invention, it is not believed to be advantageous to havethe software perform additional steps, as that would likely increasepower consumption.

In an embodiment of the invention, one of the detection schemes setforth above (e.g., half wave detection) is adapted to use an X of Ycriterion to weed out spurious detections. This can be implemented via ashift register, as usual, or by more efficient computational methods. Asdescribed above, half waves are analyzed on a window-by-window basis,and as described above (in connection with FIG. 15), the window resultsare updated on a separate analysis window interval. If the detectioncriterion (i.e., a certain number of half waves in less than a specifiedtime period) is met for any of the half waves occurring in the mostrecent window, then detection is satisfied within that window. If thatoccurs for at least X of the Y most recent windows, then the half waveanalysis tool triggers a detection. If desired, other detectionalgorithms (such as line length and area) may operate in much the sameway: if thresholds are exceeded in at least X of the Y most recentwindows, then the corresponding analysis tool triggers a detection.

Also, in the disclosed embodiment, each detection flag, after being set,remains set for a selected amount of time, allowing them to be combinedby Boolean logic (as described below) without necessarily beingsimultaneous.

As indicated above, each of the software processes set forth above(FIGS. 14-15, 18, and 21) corresponds to functions performed by the wavemorphology analysis units 912 and window analysis units 914. Each one isinitiated periodically, typically once per detection window (steps 1412and 1712/1912). The outputs from the wave morphology and window analysisunits 912 and 914, namely the flags generated in response to countedqualified half waves, accumulated line lengths, and accumulated areasare combined to identify signal event detections as functionallyillustrated in FIG. 10 and as described via flow chart in FIG. 27 below.

Patterns and sequences are identified by a system according to theinvention via finite state machines programmed into the neurostimulatordevice 310 (FIG. 3); these state machines are implemented as describedbelow with reference to FIGS. 22-26.

Referring now to FIG. 22, an unconfigured set of states and transitionevents 2210 according to the invention is illustrated. There are sixteenpossible states (numbered 0 through 15 in the illustrated example), andthere are eight possible transition events (letters A through H)permitting transition out of any of the states. In any particular statemachine according to the invention, it is not necessary to use allsixteen states or eight transition events; a subset may be used. In thedefault condition, each of the sixteen states, including an exemplaryfirst state 2212 (note that the “0”-labeled state 2214 is reserved foruse as an initial state, such as the initial state 2312 of FIG. 23), isset up such that any of the possible transition events (A-H) does notcause a transition, indicated in the Figures by a loop back to the samestate.

The states and transition events 2210 of FIG. 22 are configured into anexemplary state machine according to the invention as illustrated inFIG. 23. In particular, the state transition diagram of FIG. 23represents a state machine 2310 that is equivalent to the oneillustrated in FIG. 1. As described above, this configuration processincludes having one or more of the possible transition events (A-H, FIG.22) mapped by a system according to the invention to a detectable signalevent or other system event, so that at least one of the eight possiblesystem events causes a transition event to occur. This is preferablyfully programmable.

From an initial state 2312, signal A 2314 causes a transition to a firststate 2316, then signal B 2318 causes a transition to a second state2320, then signal C 2322 causes a transition to a detection state 2324.Likewise, from the first state 2316, signal D 2326 causes a transitionfrom the first state 2316 to a third state 2328, and then signal E 2330causes a transition into the detection state 2324. And as in FIG. 1,observing signal F 2332 from the first state 2316 causes a transition toan end state 2334.

The state machine 2310 of FIG. 23 is topologically equivalent to theexemplary state machine 110 of FIG. 1; as set forth above, unusedtransition events (i.e., transitions out) for each state used should beconfigured such that no transition occurs should the correspondingsignal event be observed. Alternatively, the unused transition eventsshould be defined such that they never occur. Unused states need not beconfigured in any particular way, as no transition into said unusedstates is possible in the normal operation of a system according to theinvention.

The state transition diagram of FIG. 24 is similar to that of FIG. 1,but with an additional (an optional) capability present in an embodimentof the present invention: individual timeout values for each state. Itwill be recognized that it is also possible to accomplish this withtime-based events (i.e., causing one or more of the eight possibletransition events to be timer-driven), but that approach is lessflexible, in that it uses up some of the limited number of transitionevents, and is not easily applied across the multiple state machineinstances employed in an embodiment of the invention (which will bedescribed in further detail below).

Referring now to FIG. 24, a state transition diagram representing anexemplary time-dependent state machine 2410 is set forth; such a statemachine is capable of being represented by a system according to theinvention, and as with FIG. 1, may represent several sequences ofconditions that may be of interest for detecting neurological events.

In particular, hypothetically (and using the nomenclature introduced inFIG. 1), if a neurological event of interest is defined by theillustrated sequence of signal events where time is important, namely a“signal A” followed in no more than thirty seconds by a “signal B”followed in no more than five seconds by a “signal C,” or alternativelysignal A followed in no more than thirty seconds by a “signal D”followed (at any time) by a “signal E,” but never includes signal Adirectly followed by a “signal F,” then the state machine of FIG. 24represents the conditions leading up to the neurological event.

In particular, starting with an initial state 2412, if signal A, 2414 isencountered, the state machine moves to a first state 2416. All of thecombinations described above begin with signal A 2414. If signal A 2414is followed by signal B 2418 within a first specified amount of time (anexemplary 30-second timeout 2419), then a second state 2420 is achieved,and if signal C 2422 is then observed before expiration of a secondspecified amount of time (an exemplary 5-second timeout 2423), then adetection state 2424 is reached, and a system according to the inventionreacts accordingly. After the system acts as desired, the state machine2410 generally will be reset to the initial state 2412 for further use.

After the first state 2416 is reached, if signal D 2426 is observedinstead of signal B 2418, then the state machine transitions to a thirdstate 2428. Following that, observation of signal E 2430 will cause thedetection state 2424 to be reached, as above. Accordingly, two possiblesequences of signal events lead to the detection state 2424: signal A2414, then signal B 2418 within thirty seconds, then signal C 2422within five seconds; or alternatively, signal A 2414, then signal D 2426within thirty seconds, then signal E 2430.

Upon attainment of the detection state, the state machine of a systemaccording to the invention has observed the combination of signals thatwas sought, and the system is actuated to respond accordingly (e.g. byproviding responsive stimulation, changing modes, recording a recordentry in the memory subsystem 526, or by performing some other action).Upon completion of the action, typically, the state machine is reset tothe initial state 2412, but alternatively, a delay may be interposed orthe state machine may be reprogrammed for detection of a differentneurological event. There are other possibilities that will be apparent.

On the other hand, if after the first state 2416 is reached, signal F2432 is encountered, then the state machine transitions to an end state2434, and a system according to the invention performs any desiredaction (which may include resetting the state machine 2410 to theinitial state 2412, either immediately or after a delay or some otheraction). In the illustrated example, two timeouts 2419 and 2423 causethe state machine to transition to the end state 2434, although itshould be recognized that timeouts can be established in a systemaccording to the invention to transition from any one state to any otherstate after a desired period of time, and that desired timeoutexpirations can be used along paths toward the detection state 2424 toensure that state transitions do not occur too quickly.

Preferably, the transitions in a state machine according to theinvention can be configured as either exclusive or nonexclusivetransitions. An exclusive transition causes one state to be exited andanother to be entered, while a nonexclusive transition is only onepossible exit from a state; that same state can be exited subsequentlyby other signal events (and tracked in parallel). Considering thisconcept as applied to the state transition diagram of FIG. 24, it willbe appreciated that the transitions out of the first state 2416 causedby signal B 2418 and signal D 2426 can be either exclusive ornonexclusive. If exclusive, then a transition via signal B 2418 willpreclude a subsequent transition via signal D 2426, and vice versa. Ifnonexclusive, then both paths are available in parallel. This approachis highly flexible and configurable; it will be described in furtherdetail below.

The states and transition events 2210 of FIG. 22 are configured into anexemplary state machine according to the invention as illustrated inFIG. 25. In particular, the state transition diagram of FIG. 25represents a state machine 2510 that is equivalent to the oneillustrated in FIG. 24.

From an initial state 2512, signal A 2514 causes a transition to a firststate 2516, then signal B 2518 causes a transition to a second state2520, then signal C 2522 causes a transition to a detection state 2524.Likewise, from the first state 2516, signal D 2526 causes a transitionfrom the first state 2516 to a third state 2528, and then signal E 2530causes a transition into the detection state 2524. And as in FIG. 24,observing signal F 2532 from the first state 2516 causes a transition toan end state 2534.

Similarly, with regard to timeouts, a first specified amount of time (anexemplary 30-second timeout 2519) causes a transition from the firststate 2516 to the end state 2534, and a second specified amount of time(an exemplary 5-second timeout 2523) causes a transition from the secondstate 2520 to the end state 2534.

The state machine 2510 of FIG. 25 is topologically equivalent to theexemplary state machine 2410 of FIG. 24; as set forth above, unusedtransition events (i.e., transitions out) for each state used should beconfigured such that no transition occurs should the event be observed.Alternatively, the unused transition events should be defined such thatthey never occur. Unused states need not be configured in any particularway, as no transition into such unused states is possible in the normaloperation of a system according to the invention.

As described above, a system according to the invention advantageouslyemploys and processes finite state machines to identify temporal andspatiotemporal patterns and sequences of signals for the detection andprediction of neurological (or other) events. This is accomplished viadata structures and constructions manipulated by the CPU 528 and memorysubsystem 526 (FIG. 5) as set forth below.

A representation of a master state machine is stored in the memorysubsystem 526 and, for reasons set forth below, is indexed by signalevent. That is, the master state machine comprises a list of the eightpossible signal events (some of which may be unused). Eachsignal-event-based entry contains, for each of the sixteen states in themaster state machine, an indication of the destination state the signalevent will cause a transition to. If the signal event is not a validexit from one or more of the states, then a loopback to the same state(meaning, as described above and as illustrated in the Figures, notransition) is indicated.

Referring back to the state transition diagram of FIG. 25, an examplemay be illustrative. Signal E 2530 only allows one transition in theentire state machine, from the third state 2528 to the detection state2524; in all other states signal E will not cause any transition(indicated in the Figures as a loop back to the same state).Accordingly, the event entry in the master state machine would berepresented as follows in Table 1:

TABLE 1 EVENT ENTRY (SIGNAL E) STARTING DESTINATION EXCLUSIVE STATESTATE TRANSITION Initial Initial Yes 1 1 Yes 2 2 Yes 3 Detection YesDetection Detection Yes End End Yes 6 6 Yes 7 7 Yes 8 8 Yes 9 9 Yes 10 10 Yes 11  11 Yes 12  12 Yes 13  13 Yes 14  14 Yes 15  15 Yes

There is an instance of the foregoing representation for each of thepossible transition events, A through H, in the master state machine.Accordingly, when a signal event is identified by a system according tothe invention (as will be described in further detail below), it is asimple and efficient operation to determine whether that event causesany transitions, and if so, from and to which states. In the disclosedembodiment, this portion of the master state machine is 80 bytes inlength: for each of the eight transition events, there are sixteenstarting states, each of which indicates a four-bit representation ofone of the sixteen possible destination states and a single bitindication of whether the transition to the destination state isexclusive. It should be noted that efficiency in storage and access, thefields of the master state machine (and other data structures describedherein) may be packed differently than specifically described; thelayout illustrated in the table above is for illustration only.

In an embodiment of the invention that includes state-based timeouts, asillustrated in FIGS. 24-25, the master state machine also includes alist of each state's possible timeout values. Accordingly, for each ofthe sixteen states there is a timeout duration value (in terms of aninteger number of “timer ticks,” described below) and a destinationstate. For instance, in the state transition diagram of FIG. 25, thesecond state 2520 has a timeout 2523 with a value of five seconds (T=5)that transitions to the end state 2534. In the disclosed embodiment, foreach state (in the example, the second state 2520), the timeout value(in the example, five seconds) is stored as an unsigned eight-bit value(where zero indicates no timeout) and the destination state (in theexample, the end state 2534) is stored in four bits. Therefore, each ofthe sixteen states requires twelve bits of timeout information, and forall sixteen states, the total is 24 bytes.

Consequently, the master state machine is represented in 88 bytes: 64bytes for the event-indexed state transition table plus 24 bytes for thestate-based timeout table.

TABLE 2 MASTER STATE MACHINE Event-Indexed State Transition Table 8events × 16 starting states × 4-bit destination = 64 bytes State-BasedTimeout Table 16 states × (8-bit time value + 4-bit destination) = 24bytesThis information, once programmed into the implantable neurostimulatordevice 310 by the programmer 612 or some other apparatus, does not needto be updated by the device 310; it serves primarily as a lookup tableas described below.

In addition to the master state machine described above, a systemaccording to the invention includes multiple instances, or “snapshots”of the state machine driven by observed signal events. Multipleinstances are needed to track parallel paths and resolve ambiguitycaused particularly by different possible exits from the initial stateand nonexclusive exits from other states in a state machine according tothe invention.

TABLE 3 INSTANCE ENTRY Current State 4 bits Overall Life Remaining 8bits State Life Remaining 8 bits

Each state machine instance includes the current state (one of sixteenpossible states, represented in four bits), the overall life remainingin the state machine instance (that is, a representation of the timeuntil the state machine instance “expires” and reverts back to itsinitial state, in eight bits of data), and the state life remaining ofthe state machine instance (a representation of the time until theinstance's current state expires and must transition to a new state,also in eight bits of data).

In one embodiment of the invention, the overall life remaining and statelife remaining values are stored in hardware-accessible registers in thedetection subsystem 522 (FIG. 5) to permit efficient decrement-and-testoperations to be performed as described below without the need forsoftware intervention.

TABLE 4 STATE MACHINE INSTANCE LIST Instance List 64 instances × 20-bitinstance entry = 160 bytes

In a preferred embodiment of the invention, there are 64 state machineinstances, which is anticipated to be sufficient for comprehensivetracking of multiple exits from the initial state and parallel paths. Aswill be described in further detail below, the “oldest” of the instancesin the instance list can be reused if necessary.

Referring now to FIG. 26, a flow chart is set forth illustrating asequence of steps performed to update the state machine instancesdescribed above. Upon identification of a system event (step 2610), thatis, a detection accomplished by the detection subsystem 522 or someother relevant event in the context of the neurostimulator device 310,as illustrated in FIGS. 27-29 below, the state machine instancesdescribed above are updated, if necessary, to account for the event.

In particular, the following procedure is followed. The first existingstate machine instance in the instance list (described above) isselected (step 2612) and evaluated (step 2614)—that is, it is updated ifnecessary (i.e., state transitions are performed as described in furtherdetail below, with reference to FIG. 30). If there are more instances inthe instance list (step 2616), the next instance in the list is selected(step 2618) and the process continues until all existing state machineinstances in the instance list have been evaluated.

If there are no more instances in the instance list (step 2616), thenthe overall life remaining values for the remaining state machineinstances that have transitioned are updated (step 2620) to reflect theyoungest instance in the same state. Specifically, as described inadditional detail below with reference to FIG. 33, if multiple instanceshave transitioned into the same state because of the system eventidentified earlier (step 2610), then there is no need to keep track ofthose multiple instances—the only difference between them is theiroverall life remaining. Accordingly, the youngest instance is kept andother instances are discarded and returned to the initial state.

Finally, if the system event identified above (step 2610) is one thatwill bring the state machine out of its initial state, then a new statemachine instance is initialized. This procedure will be described ingreater detail below with reference to FIG. 32.

It will be recognized that the process illustrated in FIG. 26 isperformed only once per relevant system event identified by a systemaccording to the invention. Consequently, the method is relativelycomputationally efficient, as the CPU 528 can remain in a relativelyinactive (“sleep”) state most of the rest of the time, awakened onlyupon system event identification (such as a signal event detection fromthe detection subsystem 522). Alternatively, much of the process of FIG.26 can be performed with custom hardware rather than the CPU 528, whichhas the potential to reduce power consumption even further.

An example of the multiple-state-machine-instance architecture of theinvention may be illustrative. Starting from an initial time (forexample, upon reset of an implantable neurostimulator device 310according to the invention), all 64 state machine instances are in theirinitial state. For purposes of this example, event detectors in thedetection subsystem 522 (FIG. 5) are updated once every second, and the“timer tick” resolution for updating state machine instance liferemaining variables is also one second.

Assume, then, that a first signal event (“signal A” 2414, FIG. 24) isdetected by the device 310, causing a system event to be asserted ateach of three consecutive timer intervals. This would not necessarily bea common real-world occurrence, but it is possible in the disclosedembodiment for the invention for the situation to occur; this simplifiedexample is presented here for clarity. Other behaviors may also bepossible, such as to treat consecutive occurrences of the same signalevent detection (either discrete detections or detections combined bypersistence as described above) as a single system event, or to have aseparate mechanism for determining when a system event is considered toend. Other possibilities will be evident to a practitioner of ordinaryskill in the relevant arts.

At the first “timer tick,” the first state machine (state machineinstance no. 1, see Table 5 below) transitions from the initial stateinto the first state 2416 (FIG. 24), the overall life remaining value isset at 100 timer ticks, and the state life remaining value is set at 30timer ticks (corresponding, in this example, to the 30-second timeout2419 of FIG. 24). At the next timer tick, the overall life remainingvalue and the state life remaining value for instance no. 1 aredecremented to 99 and 29, respectively, and since the first signal event(signal A) is still being detected, another instance is initialized:state machine instance no. 2 also transitions into the first state 2416and receives overall and state life remaining values of 100 and 30,respectively. At the next timer tick, the life remaining values forinstances 1 and 2 decrement again, and instance no. 3 is initialized asdescribed above.

After the three consecutive observations of signal A, assume that signalB 2418 (FIG. 24) is then observed. At that point, instance no. 1 willtransition to the second state 2420, the overall life remaining value isdecremented once again to 97, and the state life remaining value isinitialized at 5 (corresponding to the 5-second timeout 2423 of FIG.24). Instances 2 and 3 remain in the first state but have their liferemaining values decremented, and the remaining instances (4 through 64)are still in the initial state. This condition is illustrated in Table 5below:

TABLE 5 STATE MACHINE INSTANCE EXAMPLE Instance No. 1 2 3 4 . . . 64Current State 2 1 1 Initial . . . Initial Overall Life Remaining Value97 98 99 0 . . . 0 State Life Remaining Value 5 28 29 0 . . . 0

It should be noted that while synchronous behavior is described abovefor simplicity (i.e., life remaining values are decremented when eachevent is processed); this is only a side effect of having the same timertick interval for both signal event detection and life remainingprocessing, as described above. A system according to the inventionallows for asynchronous handling of signal event detections and timerprocessing, as will be described in additional detail below.

The system events identified above (step 2610) are generated by thedetection subsystem 522 and CPU 528 (FIG. 5) by the process illustratedin FIG. 27. This process of combining detection algorithm outputs (viaoutputs from the analysis units 912 and 914) begins with the receipt ofa timer interrupt (step 2710), which is typically generated on a regularperiodic basis to indicate the edges of successive time windows.Accordingly, in a system or method according to the disclosed embodimentof the invention, such a timer interrupt is received every 128 ms, or asotherwise programmed or designed. Then the half wave (step 2712, FIGS.14-15), line length (step 2714, FIG. 18), and area (step 2716, FIG. 21)analysis tools are evaluated with respect to the latest data generatedthereby, via the half wave analysis flag, the line length flag, and thearea flag for each active channel. The steps of checking the analysistools (steps 2712, 2714, and 2716) can be performed in any desired orderor in parallel, as they are generally not interdependent. It should benoted that the foregoing analysis tools should be checked for everyactive channel, and may be skipped for inactive detection channels.

Flags, indicating whether particular signal characteristics have beenidentified in each active channel, for each active analysis tools, arethen combined into detection channels (step 2718) as illustrated in FIG.10. In the disclosed embodiment of the invention, this operation isperformed as described in detail below with reference to FIG. 28. Eachdetection channel is a Boolean AND combination of analysis tool flagsfor a single channel, and as disclosed above, there are preferably atleast eight channels in a system according to the invention.

The flags for multiple detection channels are then combined into eventdetector flags (step 2720), which are indicative of identified signalevents or neurological events calling for action by the device,potentially a state machine transition. This process is described below,see FIG. 29, and is in general a Boolean combination of detectionchannels, if there is more than one channel per event detector.

If an event detector flag is set (step 2722), then a correspondingaction is initiated (step 2724) by the device. Actions according to theinvention can include the presentation of a warning to the patient, anapplication of therapeutic electrical stimulation, a delivery of a doseof a drug, an initiation of a device mode change, or a recording ofcertain EEG signals; it will be appreciated that there are numerousother possibilities. It is preferred, but not necessary, for actionsinitiated by a device according to the invention to be performed inparallel with the sensing and detection operations described in detailherein. It should be recognized that the application of electricalstimulation to the brain may require suspension of certain of thesensing and detection operations, as electrical stimulation signals mayotherwise feed back into the detection subsystem 522 (FIG. 5), causingundesirable results and signal artifacts.

Multiple event detector flags are possible, each one representing adifferent combination of detection channel flags. If there are furtherevent detector flags to consider (step 2726), those event detector flagsare also evaluated (step 2722) and may cause further actions by thedevice (step 2724). It should be noted that, in general, actionsperformed by the device (as in step 2724) may be in part dependent on adevice state—even if certain combinations of signal or neurologicalevents do occur, no action may be taken if the device is in an inactivestate, for example.

As described above, and as illustrated in FIG. 27 as step 2718, acorresponding set of analysis tool flags is combined into a detectionchannel flag as shown in FIG. 28 (see also FIG. 10). Initially theoutput detection channel flag is set (step 2810). Beginning with thefirst analysis tool for a particular detection channel (step 2812), ifthe corresponding analysis tool flag is not set (step 2814), then theoutput detection channel flag is cleared (step 2816).

If the corresponding analysis tool flag is set (step 2814), the outputdetection channel flag remains set, and further analysis tools for thesame channel, if any (step 2818), are evaluated. Accordingly, thiscombination procedure operates as a Boolean AND operation—if any of theenabled and active analysis tools for a particular detection channeldoes not have a set output flag, then no detection channel flag isoutput by the procedure.

A clear analysis tool flag indicates that no detection has been madewithin the flag persistence period, and for those analysis tools thatemploy an X of Y criterion, that such criterion has not been met. Incertain circumstances, it may be advantageous to also provide detectionchannel flags with logic inversion. Where a desired criterion (i.e.,combination of analysis tools) is not met, the output flag is set(rather than cleared, which is the default action). This can beaccomplished by providing selectable Boolean logic inversion (step 2820)corresponding to each event detector.

Also as described above, and as illustrated in FIG. 27 as step 2720,multiple detection channel flags are combined into a single eventdetector flag as shown in FIG. 29 (see also FIG. 8). Initially theoutput event detector flag is set (step 2910). Beginning with the firstdetection channel for a particular event detector (step 2912), if thechannel is not enabled (step 2914), then no check is made. If thechannel is enabled and the corresponding detection channel flag is notset (step 2916), then the output event detector flag is cleared (step2918) and the combination procedure exits. If the correspondingdetection channel flag is set (step 2916), the output event detectorflag remains set, and further detection channels, if any (step 2920),are evaluated after incrementing the channel being considered (step2922). Accordingly, this combination procedure also operates as aBoolean AND operation—if any of the enabled and active detectionchannels does not have a set output flag, then no event detector flag isoutput by the procedure. It should also be observed that a Boolean ORcombination of detection channels may provide useful information incertain circumstances; a software or hardware flow chart accomplishingsuch a combination is not illustrated, but could easily be created by anindividual of ordinary skill in digital electronic design or computerprogramming.

An implantable version of a system according to the inventionadvantageously has a long-term average current consumption on the orderof 10 microamps, allowing the implanted device to operate on powerprovided by a coin cell or similarly small battery for a period of yearswithout need for replacement. It should be noted, however, that asbattery and power supply configurations vary, the long-term averagecurrent consumption of a device according to the invention may also varyand still provide satisfactory performance.

The method by which individual state machine instances are evaluated(step 2614, FIG. 26) upon identification of a system event (FIG. 27) isillustrated in FIG. 30. Initially, based on the previously identifiedsystem event (step 2610, FIG. 26), the master state machine is accessedto identify what state (or states) the system event allows a transitionout of (step 3010).

If the current state of the instance being evaluated is a state that theidentified system event allows a transition out of (step 3012), then theinstance is updated (step 3014) by transitioning the instance into theappropriate new state (once again, by accessing the master statemachine) and resetting the state life remaining to the appropriate newvalue. Additional details of this step will be described below withreference to FIG. 33. The overall life remaining of the instance beingevaluated is then recorded to identify which instance is youngest (step3016), if multiple instances are in the same state. This information isused to eliminate redundant state machine instances as described abovein connection with FIG. 26. If no transition is indicated (step 3012),then the process ends.

As described in general above, each of the state machine instancesincludes a state life remaining and an overall life remaining. Theoverall life remaining value enables “expiration” of a state machineinstance if it is taking too long to match a pattern. The state liferemaining value allows any state to have a timeout value, i.e., amaximum time for a state to remain valid. Accordingly, a systemaccording to the invention includes a timer processing function enabledby the clock supply 534 (FIG. 5).

In an embodiment of the invention, the state life remaining variable andthe overall life remaining variable are both eight-bit values, each witha resolution of 64 ms (and hence a maximum value of 16 seconds).Preferably, the resolution of the state life remaining variable and theoverall life remaining variable are independently programmable from arange of values, for example 4 ms to 256 ms in power-of-two steps.

Every “timer tick,” i.e. every 64 ms if the state life remaining andoverall life remaining variables are programmed as set forth above, theprocess set forth in FIG. 31 is performed to determine whether any statemachine instances will expire or transition based on elapsed time. Forpurposes of this disclosure, it is assumed that both variables have thesame resolution. If not, it will be appreciated that state liferemaining and overall life remaining would generally be handledseparately, not together as illustrated in FIG. 31.

As described above, each instance maintains a state life remaining valueand an overall life remaining value. Upon each timer tick, a systemaccording to the invention will decrement and test those variables (step3110) in each active state machine instance. If one or more of the statelife remaining values have expired (step 3112), i.e., reached zero, thecorresponding state machine instances are updated (step 3114) bytransitioning the instances into the appropriate new states (once again,by accessing the master state machine) and resetting the state liferemaining variable to the appropriate new value. Additional details ofthis step will be described below with reference to FIG. 33. If one ormore of the overall life remaining values have expired (step 3116), orreached zero, those instances are reset to the initial state (step3118).

When an end state is reached (e.g. the end state 2534, FIG. 25), eithervia timeout or system event, a system according to the invention ispreferably programmable to perform any desired action. For example, inan embodiment of the invention, the system may be programmed to record adiagnostic record in the memory subsystem 526 (FIG. 5), delay for a fewseconds, and reset to the initial state. Other possibilities will beevident and are considered to be within the scope of the presentinvention.

Similarly, when a detection state is reached (e.g. the detection state2524, FIG. 25), a system according to the invention is programmable toperform an action, typically the delivery of therapy or some mode changerelated to treatment. For example, electrical stimulation (tailored tothe type of detection that was made) may be delivered, or the system(and particularly the detection subsystem 522) may be put into aheightened state of alert for subsequent detections. Other possibilitiesare set forth herein, and will be apparent to a practitioner of ordinaryskill. Such variations and others are deemed to be within the scope ofthe present invention.

Transitions out of the state machine's initial state are handledaccording to the process illustrated in FIG. 32, which is performedafter every system event is identified (at step 2622, FIG. 26).

If a previously identified system event (step 2610, FIG. 26) allows atransition out of the master state machine's initial state (step 3210),then it is first determined whether there is an unused state machineinstance in the instance list (step 3212). An unused state machineinstance is one in its initial state; while a state machine instance isin the initial state, the state life remaining and overall liferemaining variables are not meaningful, and hence, they are not updated.

If an unused state machine instance is available, then one is identified(step 3214), selected for use (step 3216), and initialized (step 3218)by making the appropriate transition out of the initial state (asindicated by the master state machine), and setting the overall liferemaining and state life remaining variables to their appropriate values(as also indicated by the master state machine).

If no unused state machine instance is available, then the state machineinstance with the smallest overall life remaining value (i.e., closestto expiration) is identified (step 3220), selected for use (step 3222),and initialized (step 3218) as before. Accordingly, this allows the useof a shorter list of state machine instances than would otherwise bepossible, where all possible permutations of overall life remainingvalues are preserved.

A state machine instance is updated (as in step 3014, FIG. 30, and step3114, FIG. 31) as illustrated in the flow chart of FIG. 33.

The current state of the current state machine instance is firstidentified (step 3310). If this is the first transition into thedestination state (step 3312) for the system event being processed(identified at step 2610, FIG. 26), then the appropriate transition isperformed (step 3314, illustrated in detail in FIG. 34), based oninformation in the master state machine, and the overall life remainingvariable of the current state machine instance is saved (step 3316) forthis system event and this target state in the memory subsystem 526(FIG. 5); it will be used later (it is generally stored in a temporarystorage area, and only for the duration of the current pass through theprocess of FIG. 26).

On the other hand, if this is not the first transition out of thecurrent state (step 3312), and other state machine instances have madethe same transitions previously (during the servicing of the currentsystem event), then the overall life remaining of the current statemachine instance is compared to the saved (youngest) overall liferemaining (from step 3316, above). If the current state machine instanceis younger (step 3318), then the saved overall life remaining is updatedto reflect the younger overall life remaining (step 3320), and thecurrent state machine instance is reset to an unused state (step 3322).If the current state machine instance is not newer, then the savedoverall life remaining is not changed and the current state machineinstance is initialized (step 3322). As set forth above, the saved liferemaining value is used to update only one of the state machineinstances, while others in the same state (but with smaller overall liferemaining values) are discarded. See FIG. 26, step 2620.

Transitions from state to state are performed in an embodiment of theinvention according to the process illustrated in FIG. 34. Initially theproper transition path in the master state machine is identified (step3410), thereby selecting the proper destination state and exclusivitystatus associated with the current system event and current state. Ifthe transition path is an exclusive one (step 3412) as indicated in themaster state machine, then the current state of the instance beingprocessed is updated to reflect the destination state (step 3414) andthe state life remaining is also updated to the appropriate value (step3416).

On the other hand, if the transition is nonexclusive (step 3412), aseparate instance is spawned as set forth below. If there is an unusedinstance in the instance list (step 3418), i.e. one that is in theinitial state, that unused instance is identified (step 3420) andselected (step 3422). The selected instance is then initialized (step3424) to appropriate values: the current state of the selected instanceis set to reflect the destination state (selected at step 3410, above),the state life remaining is set appropriately, and the overall liferemaining is set to the same value as that of the original instance (theinstance having the transition that is spawning the new instance).

If there is no unused instance (step 3418), then the oldest existinginstance is identified (step 3426) and selected for reuse (step 3428).The reused instance is then initialized as described above.

Consequently, then, the result of a nonexclusive transition is that twoinstances are created out of a single instance's transition. Oneinstance remains in its current state (and its life remaining values areunchanged), while the other instance makes the transition. Accordingly,returning to the exemplary state machine of FIG. 1, if the signal B 118and signal D 126 transitions out of the first state 116 arenonexclusive, then it is possible to detect the sequence A>B>D>E as avalid detection sequence (upon detection of signal B 118, one instancetransitions to the second state 120 while one remains in the first state116). There are other possibilities as well. That is, the occurrence ofsignal B 118 is not the exclusive path out of the first state 116. Oneconstructive approach to understanding the utility of nonexclusivetransitions is to think of the A>B>D>E sequence set forth above asA>(B)>D>E, where the operative detection sequence is A>D>E, as expresslyillustrated in FIG. 1—where the intervening signal B 118 is detected butdoes not disrupt the detection sequence. It will be appreciated that theapproach set forth herein provides a great deal of flexibility.

If the transitions of FIG. 1 are exclusive, then A>B>D>E will not bedetected; the transition caused by signal B 118 from the first state 116to the second state 120 precludes the subsequent transition into thethird state 128 when signal D 126 is encountered. Accordingly, detectingsignal B 118 will disrupt the A>D>E pattern, and detecting signal D 126will disrupt the A>B>C pattern.

Both approaches have their advantages; as described herein a systemaccording to the invention can be selectively configured to implementstate machines including both exclusive and nonexclusive transitions asclinically desired.

It should be noted that transitions to an end state, such as thetransition caused by signal F 132 of FIG. 1, should generally beexclusive—there is believed to be little reason to end a newly-spawnedinstance while allowing another instance to continue. Similarly, wherethere is only a single valid transition out of a state, it shouldgenerally be configured as exclusive.

It should be observed that while the foregoing detailed description ofvarious embodiments of the present invention is set forth in somedetail, the invention is not limited to those details and an implantableneurostimulator or neurological disorder detection device made accordingto the invention can differ from the disclosed embodiments in numerousways. In particular, it will be appreciated that embodiments of thepresent invention may be employed in many different applications todetect anomalous neurological patterns and sequences in at least oneportion of a patient's brain. It will be appreciated that the functionsdisclosed herein as being performed by hardware and software,respectively, may be performed differently in an alternative embodiment.It should be further noted that functional distinctions are made abovefor purposes of explanation and clarity; structural distinctions in asystem or method according to the invention may not be drawn along thesame boundaries.

It will be apparent that the exemplary state machines set forth hereinare intended to be illustrative and not limiting. It is possible toemploy more or fewer than sixteen states or more or fewer than eightpossible transition events, or to encode timeouts differently, to namebut a few possibilities. It should be recognized that increased storagespace will be required for increases in either the number of transitionevents or the number of states, but little performance penalty will beincurred. Similarly, more or fewer than 64 state machine instances canbe employed by a system according to the invention. Additional executiontime may be required to process additional instances.

The appropriate scope hereof is deemed to be in accordance with theclaims as set forth below.

What is claimed is:
 1. An implantable medical device, comprising: a sensing subsystem configured to sense electrical activity from a patient's brain; a detection subsystem configured to detect a set of signal events based on the sensed electrical activity; a configurable finite state machine comprising: a representation of a set of states; a representation of a set of transition events, wherein an occurrence of a first transition event of the set of transition events causes a first transition out of a first state, the first transition being one of an exclusive transition from the first state or a non-exclusive transition from the first state, and wherein an occurrence of a second transition event of the set of transition events may cause a second transition out of the first state; and a representation of the set of signal events, wherein a first detected signal event of the set of signal events is mapped to the first transition event, a second detected signal event of the set of signal events is mapped to the second transition event, wherein the first detected signal event, once mapped to the first transition event, causes the first transition to occur, and the second detected signal event, once mapped to the second transition event, causes the second transition to occur when the first transition is a non-exclusive transition, and to not occur when the first transition is an exclusive transition; a central processing unit configured, in conjunction with the configurable finite state machine, to determine whether at least two individual detected signal events of the set of signal events occur in at least one of a predetermined pattern and sequence representative of a neurological event, wherein the central processing unit selects a response, from a predetermined menu of possible responses, whenever the predetermined pattern and sequence of the at least two individual neurological events is determined to have occurred.
 2. The implantable medical device of claim 1, wherein the predetermined sequence includes requiring that a second signal event occurs within a predetermined time period of a first signal event.
 3. The implantable medical device of claim 1, wherein the detection subsystem detects signal events based on morphological characteristics of the sensed electrical activity.
 4. The implantable medical device of claim 3, wherein the morphological characteristics are half waves.
 5. The implantable medical device of claim 1, wherein the detection subsystem detects signal events based on characteristics of sensed electrical activity normalized to a particular window of time of a predetermined length.
 6. The implantable medical device of claim 5, wherein the time window-normalized characteristics are the sum of the line lengths in the window or the total area under the curve in the window.
 7. The implantable medical device of claim 1, wherein the detection subsystem detects signal events based on a combination of morphological characteristics of the sensed electrical activity and characteristics of the sensed electrical activity normalized to a particular window of time of a predetermined length.
 8. The implantable medical device of claim 1, wherein the menu of possible responses includes one or more of registering detection of a predefined neurological condition, initiating a therapy, and generating a warning.
 9. The implantable medical system of claim 1, further comprising at least one implantable electrode coupled to the stimulation subsystem and adapted to deliver electrical stimulation to the patient.
 10. The implantable medical system of claim 9, wherein the at least one implantable electrode adapted to deliver electrical stimulation to the patient is also coupled to the sensing subsystem and adapted to sense the electrical activity from the patient. 